Review
. 2017 Nov; 6(11):e1356148.
doi: 10.1080/2162402X.2017.1356148.

The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis

Emma J de Ruiter 1 Marc L Ooft 1 Lot A Devriese 2 Stefan M Willems 1 
Affiliations
  • PMID: 29147608
  •     60 References
  •     101 citations

Abstract

Background - The presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with an improved prognosis and a better response to therapy in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic value of T cells in head and neck squamous cell carcinoma (HNSCC). Methods - In a systematic review, Pubmed and Embase were searched for publications that investigated the prognostic value of T cells in HNSCC. A meta-analysis was performed including all studies assessing the association between CD3+, CD4+, CD8+, and FoxP3+ TILs and overall survival (OS), disease-free survival (DFS), or locoregional control (LRC). Results - A pooled analysis indicated a favorable, prognostic role for CD3+ TILs (HR 0.64 (95%CI 0.47-0.85) for OS, HR 0.63 (95%CI 0.49-0.82) for DFS) and CD8+ TILs (HR 0.67 (95%CI 0.58-0.79) for OS, HR 0.50 (95%CI 0.37-0.68) for DFS, and HR 0.82 (95%CI 0.70-0.96) for LRC) in the clinical outcome of HNSCC. FoxP3+ TILs were also associated with better OS (HR 0.80 (95%CI 0.70-0.92)). Conclusion - This systematic review and meta-analysis confirmed the favorable, prognostic role of CD3+ and CD8+ T cell infiltration in HNSCC patients and found an association between FoxP3+ TILs and improved overall survival. Future studies using homogeneous patient cohorts with regard to tumor subsite, stage and treatment are necessary to provide more insight in the predictive value of TILs in HNSCC.

Keywords: T cells; head and neck squamous cell carcinoma (HNSCC); prognostic biomarkers; systematic review; tumor infiltrating lymphocytes (TILs).

Burnet oration: dendritic cells: multiple subtypes, multiple origins, multiple functions.
K Shortman.
Immunol Cell Biol, 2000 Apr 13; 78(2). PMID: 10762417
Review.
Objective measurement and clinical significance of TILs in non-small cell lung cancer.
Kurt A Schalper, Jason Brown, +5 authors, David L Rimm.
J Natl Cancer Inst, 2015 Feb 05; 107(3). PMID: 25650315    Free PMC article.
Highly Cited.
Genetically modified T cells in cancer therapy: opportunities and challenges.
Michaela Sharpe, Natalie Mount.
Dis Model Mech, 2015 Jun 03; 8(4). PMID: 26035842    Free PMC article.
Review.
Tailored Tumor Immunogenicity Reveals Regulation of CD4 and CD8 T Cell Responses against Cancer.
Sarah Knocke, Bettina Fleischmann-Mundt, +4 authors, Norman Woller.
Cell Rep, 2016 Nov 24; 17(9). PMID: 27880900
Practical methods for incorporating summary time-to-event data into meta-analysis.
Jayne F Tierney, Lesley A Stewart, +2 authors, Matthew R Sydes.
Trials, 2007 Jun 09; 8. PMID: 17555582    Free PMC article.
Highly Cited.
Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx.
William H Westra, James S Lewis.
Head Neck Pathol, 2017 Mar 02; 11(1). PMID: 28247229    Free PMC article.
T regulatory cell markers in oral squamous cell carcinoma: Relationship with survival and tumor aggressiveness.
Geane Moreira, Lívia Bonfim Fulgêncio, +3 authors, Tarcília Aparecida DA Silva.
Oncol Lett, 2010 Jan 01; 1(1). PMID: 22966269    Free PMC article.
Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients.
H R Ali, E Provenzano, +18 authors, C Caldas.
Ann Oncol, 2014 Jun 12; 25(8). PMID: 24915873
Highly Cited.
A model for predicting clinical outcome in patients with human papillomavirus-positive tonsillar and base of tongue cancer.
Nikolaos Tertipis, Ulf Hammar, +13 authors, Tina Dalianis.
Eur J Cancer, 2015 May 31; 51(12). PMID: 26025766
Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study.
Gregory T Wolf, Douglas B Chepeha, +4 authors, University of Michigan Head and Neck SPORE Program.
Oral Oncol, 2014 Oct 07; 51(1). PMID: 25283344    Free PMC article.
CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma.
Cecilia Nordfors, Nathalie Grün, +10 authors, Tina Dalianis.
Eur J Cancer, 2013 Apr 11; 49(11). PMID: 23571147
HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies.
Rüveyda Dok, Sandra Nuyts.
Cancers (Basel), 2016 Apr 05; 8(4). PMID: 27043631    Free PMC article.
Review.
Regulatory T-cell infiltration in tongue squamous cell carcinoma.
Hiroyuki Hanakawa, Yorihisa Orita, +9 authors, Tadashi Yoshino.
Acta Otolaryngol, 2014 Jun 13; 134(8). PMID: 24921153
Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.
Luc Bron, Camilla Jandus, +4 authors, Jean-Paul Rivals.
Int J Cancer, 2012 Jul 21; 132(3). PMID: 22815199
PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients.
Hye Ryun Kim, Sang-Jun Ha, +10 authors, Sun Och Yoon.
Sci Rep, 2016 Nov 15; 6. PMID: 27841362    Free PMC article.
Highly Cited.
Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
David Moher, Larissa Shamseer, +6 authors, PRISMA-P Group.
Syst Rev, 2015 Jan 03; 4. PMID: 25554246    Free PMC article.
Highly Cited.
Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma.
Yoshiko Watanabe, Fuminori Katou, +3 authors, Kenji Hashimoto.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010 Mar 23; 109(5). PMID: 20303300
Search filters for finding prognostic and diagnostic prediction studies in Medline to enhance systematic reviews.
Geert-Jan Geersing, Walter Bouwmeester, +4 authors, Karel Moons.
PLoS One, 2012 Mar 07; 7(2). PMID: 22393453    Free PMC article.
Standard, and novel cytotoxic and molecular-targeted, therapies for HNSCC: an evidence-based review.
David Murdoch.
Curr Opin Oncol, 2007 Apr 07; 19(3). PMID: 17414639
Review.
Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma.
E Zancope, N L Costa, +5 authors, A C Batista.
J Oral Pathol Med, 2009 Sep 17; 39(2). PMID: 19754647
Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer.
Anders Näsman, Mircea Romanitan, +7 authors, Torbjörn Ramqvist.
PLoS One, 2012 Jun 16; 7(6). PMID: 22701698    Free PMC article.
Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma.
Jing-Jing Song, Si-Jia Zhao, +6 authors, Zhi Wang.
BMC Cancer, 2016 Jul 28; 16. PMID: 27457382    Free PMC article.
Expression of EPHRIN-A1, SCINDERIN and MHC class I molecules in head and neck cancers and relationship with the prognostic value of intratumoral CD8+ T cells.
Meriem Hasmim, Cécile Badoual, +10 authors, Salem Chouaib.
BMC Cancer, 2013 Dec 18; 13. PMID: 24330498    Free PMC article.
A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency.
Simone Punt, Emilie A C Dronkers, +8 authors, Ekaterina S Jordanova.
Cancer Immunol Immunother, 2016 Feb 24; 65(4). PMID: 26899388    Free PMC article.
Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma.
Maria Vassilakopoulou, Margaritis Avgeris, +11 authors, Amanda Psyrri.
Clin Cancer Res, 2015 Sep 27; 22(3). PMID: 26408403
Highly Cited.
Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.
P Balermpas, Y Michel, +5 authors, E Fokas.
Br J Cancer, 2013 Oct 17; 110(2). PMID: 24129245    Free PMC article.
Highly Cited.
Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study.
Joshua Bauml, Tanguy Y Seiwert, +15 authors, Robert Haddad.
J Clin Oncol, 2017 Mar 23; 35(14). PMID: 28328302    Free PMC article.
Highly Cited.
Tumor microenvironment in head and neck squamous cell carcinoma.
Joseph M Curry, John Sprandio, +4 authors, Madalina Tuluc.
Semin Oncol, 2014 May 03; 41(2). PMID: 24787294
Highly Cited.
CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck.
Astrid De Meulenaere, Tijl Vermassen, +5 authors, Sylvie Rottey.
Pathobiology, 2016 Jul 09; 83(6). PMID: 27389010
Regulatory T cells in cancer.
Dimitrios Mougiakakos, Aniruddha Choudhury, +2 authors, C Christian Johansson.
Adv Cancer Res, 2010 Apr 20; 107. PMID: 20399961
Highly Cited. Review.
Infiltrating lymphocytes and human papillomavirus-16--associated oropharyngeal cancer.
Derrick Wansom, Emily Light, +15 authors, UM Head Neck SPORE Program.
Laryngoscope, 2011 Dec 21; 122(1). PMID: 22183632    Free PMC article.
Prognostic Significance of Stromal Versus Intratumoral Infiltrating Lymphocytes in Different Subtypes of Breast Cancer Treated With Cytotoxic Neoadjuvant Chemotherapy.
Thaer Khoury, Vidya Nagrale, +3 authors, Song Yao.
Appl Immunohistochem Mol Morphol, 2017 Feb 12; 26(8). PMID: 28187033    Free PMC article.
Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors.
Pauline M W van Kempen, Rob Noorlag, +6 authors, Stefan M Willems.
Cancer Immunol Immunother, 2016 Mar 20; 65(5). PMID: 26993499    Free PMC article.
Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.
Christoph Reissfelder, Slava Stamova, +14 authors, Philipp Beckhove.
J Clin Invest, 2015 Jan 07; 125(2). PMID: 25562322    Free PMC article.
Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma.
Dominik Pretscher, Luitpold V Distel, +3 authors, Gerald Niedobitek.
BMC Cancer, 2009 Aug 25; 9. PMID: 19698134    Free PMC article.
Control of regulatory T cell development by the transcription factor Foxp3.
Shohei Hori, Takashi Nomura, Shimon Sakaguchi.
Science, 2003 Jan 11; 299(5609). PMID: 12522256
Highly Cited.
Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma.
K Oguejiofor, J Hall, +6 authors, C M L West.
Br J Cancer, 2015 Aug 28; 113(6). PMID: 26313665    Free PMC article.
Importance of FOXP3 in prognosis and its relationship with p16 in tonsillar squamous cell carcinoma.
Kwonoh Park, Kyung Ja Cho, +2 authors, Sung-Bae Kim.
Anticancer Res, 2013 Dec 11; 33(12). PMID: 24324115
Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo.
T Nishimura, K Iwakabe, +8 authors, A Ohta.
J Exp Med, 1999 Sep 08; 190(5). PMID: 10477547    Free PMC article.
Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.
Bin Shang, Yao Liu, Shu-juan Jiang, Yi Liu.
Sci Rep, 2015 Oct 16; 5. PMID: 26462617    Free PMC article.
Highly Cited. Systematic Review.
Effector CD4 and CD8 T cells and their role in the tumor microenvironment.
Sine Hadrup, Marco Donia, Per Thor Straten.
Cancer Microenviron, 2012 Dec 18; 6(2). PMID: 23242673    Free PMC article.
Composition of inflammatory cells regulating the response to concurrent chemoradiation therapy for HPV (+) tonsil cancer.
Yoon Se Lee, Ji Young Park, +6 authors, Sang Yoon Kim.
Oral Oncol, 2015 Oct 18; 51(12). PMID: 26475063
Regulatory T cells and immune tolerance.
Shimon Sakaguchi, Tomoyuki Yamaguchi, Takashi Nomura, Masahiro Ono.
Cell, 2008 May 31; 133(5). PMID: 18510923
Highly Cited. Review.
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
Robert L Ferris, George Blumenschein, +20 authors, Maura L Gillison.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718784    Free PMC article.
Highly Cited.
FOXP3 subcellular localization predicts recurrence in oral squamous cell carcinoma.
Donald T Weed, Gail Walker, +4 authors, Paolo Serafini.
PLoS One, 2013 Aug 27; 8(8). PMID: 23977174    Free PMC article.
Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease.
Luitpold V Distel, Rainer Fickenscher, +7 authors, Gerhard G Grabenbauer.
Oral Oncol, 2009 Jul 07; 45(10). PMID: 19576838
Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma.
Sm Russell, Te Angell, +5 authors, Al Epstein.
Head Neck Oncol, 2013 Feb 27; 5(3). PMID: 24723971    Free PMC article.
The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis.
M J M Gooden, G H de Bock, +2 authors, H W Nijman.
Br J Cancer, 2011 Jun 02; 105(1). PMID: 21629244    Free PMC article.
Highly Cited. Systematic Review.
The role of tumour FoxP3 as prognostic marker in different subtypes of head and neck cancer.
Patrick Weller, Agnes Bankfalvi, +6 authors, Claudia A Dumitru.
Eur J Cancer, 2014 Mar 19; 50(7). PMID: 24630394
Assessing bias in studies of prognostic factors.
Jill A Hayden, Danielle A van der Windt, +2 authors, Claire Bombardier.
Ann Intern Med, 2013 Feb 20; 158(4). PMID: 23420236
Highly Cited.
CD4+/CD8+ macrophages infiltrating at inflammatory sites: a population of monocytes/macrophages with a cytotoxic phenotype.
Tomohisa Baba, Akihiro Ishizu, +5 authors, Masanori Kasahara.
Blood, 2005 Nov 05; 107(5). PMID: 16269616
CD19(+)IL-10(+) regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4(+) T cells to CD4(+)Foxp3(+) regulatory T cells.
Xi Zhou, Yu-Xiong Su, +2 authors, Gui-Qing Liao.
Oral Oncol, 2015 Dec 04; 53. PMID: 26631955
Prognostic value of CD25 expression on lymphocytes and tumor cells in squamous-cell carcinoma of the head and neck.
David Loose, Alberto Signore, +4 authors, Christophe Van de Wiele.
Cancer Biother Radiopharm, 2008 Feb 27; 23(1). PMID: 18298326
Head and neck cancer.
Athanassios Argiris, Michalis V Karamouzis, David Raben, Robert L Ferris.
Lancet, 2008 May 20; 371(9625). PMID: 18486742    Free PMC article.
Highly Cited. Review.
Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma.
Nghia Nguyen, Emily Bellile, +15 authors, Head and Neck SPORE Program Investigators.
Head Neck, 2016 Feb 18; 38(7). PMID: 26879675    Free PMC article.
Highly Cited.
Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer.
M J Ward, S M Thirdborough, +14 authors, G J Thomas.
Br J Cancer, 2013 Oct 31; 110(2). PMID: 24169344    Free PMC article.
Highly Cited.
Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the identification of high-risk patients for developing synchronous cancers over upper aerodigestive tract.
Wen-Lun Wang, Wei-Lun Chang, +5 authors, Bor-Shyang Sheu.
Oral Oncol, 2015 May 12; 51(7). PMID: 25958829
Cancer immunology.
Olivera J Finn.
N Engl J Med, 2008 Jun 21; 358(25). PMID: 18565863
Highly Cited. Review.
The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas.
Christina S Kong, Balasubramanian Narasimhan, +5 authors, Quynh-Thu Le.
Int J Radiat Oncol Biol Phys, 2009 May 12; 74(2). PMID: 19427557    Free PMC article.
CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful.
Hye-Jung Kim, Harvey Cantor.
Cancer Immunol Res, 2014 Apr 30; 2(2). PMID: 24778273
Highly Cited. Review.
The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma.
Sarah Rosanne Ottenhof, Rosa Sanne Djajadiningrat, +7 authors, Ekaterina Straschimirova Jordanova.
Front Immunol, 2018 Jun 27; 9. PMID: 29942303    Free PMC article.
EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer.
Wenbo Ma, Fernando Concha-Benavente, +4 authors, Sjoerd H van der Burg.
PLoS One, 2018 Sep 08; 13(9). PMID: 30192802    Free PMC article.
Immune Checkpoint Inhibition in Head and Neck Cancer.
Martin David Forster, Michael-John Devlin.
Front Oncol, 2018 Sep 14; 8. PMID: 30211111    Free PMC article.
Review.
Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy.
Steven F Gameiro, Farhad Ghasemi, +4 authors, Saman Maleki Vareki.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288365    Free PMC article.
[Prognostic significance of immune cell infiltrates in tumor pathology].
D-C Wagner, W Roth.
Pathologe, 2018 Oct 24; 39(6). PMID: 30350175
Review.
Metformin Clinical Trial in HPV+ and HPV- Head and Neck Squamous Cell Carcinoma: Impact on Cancer Cell Apoptosis and Immune Infiltrate.
Joseph M Curry, Jennifer Johnson, +14 authors, Ubaldo Martinez-Outschoorn.
Front Oncol, 2018 Oct 27; 8. PMID: 30364350    Free PMC article.
Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma.
Douglas J Hartman, Fahad Ahmad, +2 authors, Liron Pantanowitz.
Oral Oncol, 2018 Nov 10; 86. PMID: 30409313    Free PMC article.
Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients.
Katalin Balázs, Enikő Kis, +12 authors, Katalin Lumniczky.
Cancers (Basel), 2019 Sep 11; 11(9). PMID: 31500214    Free PMC article.
CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer.
Alessia Echarti, Markus Hecht, +4 authors, Luitpold Distel.
Cancers (Basel), 2019 Sep 25; 11(9). PMID: 31546872    Free PMC article.
Immune infiltration in nasopharyngeal carcinoma based on gene expression.
Meng-Si Luo, Guan-Jiang Huang, Bao-Xinzi Liu.
Medicine (Baltimore), 2019 Oct 03; 98(39). PMID: 31574860    Free PMC article.
Prognostic value and clinicopathological roles of phenotypes of tumour-associated macrophages in colorectal cancer.
Yamei Zhao, Xiaoxu Ge, +3 authors, Lifeng Sun.
J Cancer Res Clin Oncol, 2019 Oct 28; 145(12). PMID: 31650222
Review.
Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma.
Valerie Cristina, Ruth Gabriela Herrera-Gómez, +2 authors, Marco Siano.
Int J Mol Sci, 2019 Nov 02; 20(21). PMID: 31671550    Free PMC article.
Review.
The Impact of Javanica Oil Emulsion Injection on Chemotherapy Efficacy and Cellular Immune Indicators in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis.
Huilin Xu, Zhucheng Yin, Anbing He, Dedong Cao.
Evid Based Complement Alternat Med, 2019 Nov 30; 2019. PMID: 31781280    Free PMC article.
Review.
The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation.
Dan Yu, Xueshibojie Liu, +6 authors, Lianji Wen.
Cell Commun Signal, 2019 Dec 29; 17(1). PMID: 31881947    Free PMC article.
Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer.
Liye Zhou, Tenny Mudianto, +2 authors, Ravindra Uppaluri.
Clin Cancer Res, 2019 Sep 29; 26(1). PMID: 31562203    Free PMC article.
CDK6 inhibits lymphoid cell infiltration and represents a prognostic marker in HPV+ squamous cell carcinoma of head and neck.
Chuanhao Tang, Li Lin, +7 authors, Jun Liang.
Chin J Cancer Res, 2020 Jan 18; 31(6). PMID: 31949392    Free PMC article.
Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma.
Yangyang She, Xiangbo Kong, +5 authors, Silian Fang.
Cancer Cell Int, 2020 Jan 29; 20. PMID: 31988638    Free PMC article.
Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation.
Martijn van der Heijden, Paul B M Essers, +12 authors, Conchita Vens.
Front Oncol, 2020 Jan 31; 9. PMID: 31998639    Free PMC article.
Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma.
S S Jeske, P J Schuler, +5 authors, M C Wigand.
Immun Ageing, 2020 Feb 23; 17. PMID: 32082401    Free PMC article.
Clinical update on head and neck cancer: molecular biology and ongoing challenges.
Elham Alsahafi, Katheryn Begg, +4 authors, Mahvash Tavassoli.
Cell Death Dis, 2019 Jul 17; 10(8). PMID: 31308358    Free PMC article.
Highly Cited. Review.
[Oncoimmunology in old age].
M C Wigand, S Jeske, +4 authors, P J Schuler.
HNO, 2019 Sep 29; 68(3). PMID: 31559466
Review.
Prognostic Value of Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma.
Matthew E Spector, Emily Bellile, +10 authors, University of Michigan Head and Neck SPORE Program.
JAMA Otolaryngol Head Neck Surg, 2019 Sep 06; 145(11). PMID: 31486841    Free PMC article.
A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts Disease Free Survival in Oral Squamous Cell Carcinoma.
Muhammad Shaban, Syed Ali Khurram, +6 authors, Nasir M Rajpoot.
Sci Rep, 2019 Sep 19; 9(1). PMID: 31527658    Free PMC article.
Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma.
M Oliva, A Spreafico, +4 authors, L L Siu.
Ann Oncol, 2018 Nov 22; 30(1). PMID: 30462163    Free PMC article.
Review.
Tumor-infiltrating CD8+ T-cell density is an independent prognostic marker for oral squamous cell carcinoma.
Shota Shimizu, Hiroyoshi Hiratsuka, +9 authors, Akihiro Miyazaki.
Cancer Med, 2019 Jan 03; 8(1). PMID: 30600646    Free PMC article.
Evaluating CAR-T Cell Therapy in a Hypoxic 3D Tumor Model.
Yuta Ando, Elizabeth L Siegler, +7 authors, Keyue Shen.
Adv Healthc Mater, 2019 Feb 09; 8(5). PMID: 30734529    Free PMC article.
Tissue-infiltrating immune cells as prognostic markers in oral squamous cell carcinoma: a systematic review and meta-analysis.
Elin Hadler-Olsen, Anna Maria Wirsing.
Br J Cancer, 2019 Feb 28; 120(7). PMID: 30808992    Free PMC article.
Systematic Review.
Non-murine models to investigate tumor-immune interactions in head and neck cancer.
Carlos Rossa, Nisha J D'Silva.
Oncogene, 2019 Mar 16; 38(25). PMID: 30872793    Free PMC article.
Review.
Inhibition of EphB4-Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers.
Shilpa Bhatia, Ayman Oweida, +12 authors, Sana D Karam.
Cancer Res, 2019 Mar 22; 79(10). PMID: 30894369    Free PMC article.
Clinicohistopathological implications of MMP/VEGF expression in retinoblastoma: a combined meta-analysis and bioinformatics analysis.
Jingyi Zhu, Xi Zhang, +2 authors, Jian Ye.
J Transl Med, 2019 Jul 18; 17(1). PMID: 31311559    Free PMC article.
Treatment outcomes for one-stage concurrent surgical resection and reconstruction of synchronous esophageal and head and neck squamous cell carcinoma.
Yu-Hsuan Lin, Chun-Yen Ou, +3 authors, Yi-Ting Yen.
Eur Arch Otorhinolaryngol, 2019 Jul 25; 276(10). PMID: 31332550
PLCε1 suppresses tumor growth by regulating murine T cell mobilization.
M Strazza, K Adam, +2 authors, A Mor.
Clin Exp Immunol, 2019 Dec 24; 200(1). PMID: 31867717    Free PMC article.
Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis.
Xiuzhi Zhang, Fenglan Gao, +3 authors, Hongmei Yang.
J Cancer, 2020 Apr 02; 11(11). PMID: 32231717    Free PMC article.
Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors.
Emma J de Ruiter, Reinout H de Roest, +4 authors, Stefan M Willems.
Cancer Immunol Immunother, 2020 Jan 26; 69(4). PMID: 31980916    Free PMC article.
Relationship between local and systemic inflammatory response and prognosis in laryngeal squamous cell carcinoma.
Ulku Kucuk, Sumeyye Ekmekci, +2 authors, Ibrahim Cukurova.
North Clin Istanb, 2020 Apr 08; 7(2). PMID: 32259041    Free PMC article.
The role of pretreatment prognostic nutritional index in esophageal cancer: A meta-analysis.
Yibo Xue, Xiang Zhou, +2 authors, Jinhua Luo.
J Cell Physiol, 2019 Jul 28; 234(11). PMID: 31344989    Free PMC article.
Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date.
Michael G McCusker, Dennis Orkoulas-Razis, Ranee Mehra.
Onco Targets Ther, 2020 Apr 21; 13. PMID: 32308436    Free PMC article.
Review.
The prognostic role of NK cells and their ligands in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.
Sangeeta K Bisheshar, Emma J De Ruiter, Lot A Devriese, Stefan M Willems.
Oncoimmunology, 2020 May 05; 9(1). PMID: 32363116    Free PMC article.
Systematic Review.
Prognostic Value of Tumor-Infiltrating Lymphocytes Differs Depending on Lymphocyte Subsets in Esophageal Squamous Cell Carcinoma: An Updated Meta-Analysis.
Jiatao Hao, Meng Li, +5 authors, Shuai Wang.
Front Oncol, 2020 May 16; 10. PMID: 32411602    Free PMC article.
Systematic Review.
MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling.
Hoi-Lam Ngan, Yuchen Liu, +15 authors, Vivian Wai Yan Lui.
Life Sci Alliance, 2020 May 10; 3(6). PMID: 32381551    Free PMC article.
CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma.
Nasser Al-Rajhi, Hussein Soudy, +4 authors, Hazem Ghebeh.
BMC Cancer, 2020 Mar 23; 20(1). PMID: 32199452    Free PMC article.
Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.
Min Hwan Kim, Jae-Hwan Kim, +15 authors, Hye Ryun Kim.
Br J Cancer, 2020 Apr 03; 122(11). PMID: 32235905    Free PMC article.
Tumor immune microenvironment in head and neck cancers.
Samantha M Y Chen, Alexandra L Krinsky, +3 authors, Jing H Wang.
Mol Carcinog, 2020 Feb 06; 59(7). PMID: 32017286    Free PMC article.
Review.
The role of transforming growth factor-beta in immune suppression and chronic inflammation of squamous cell carcinomas.
Alexander A Strait, Xiao-Jing Wang.
Mol Carcinog, 2020 Apr 18; 59(7). PMID: 32301180    Free PMC article.
Review.
Metastatic disease in head & neck oncology.
Paolo Pisani, Mario Airoldi, +34 authors, Angelo Zigliani.
Acta Otorhinolaryngol Ital, 2020 May 30; 40(SUPPL. 1). PMID: 32469009    Free PMC article.
Review.
Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy.
Joshua D Horton, Hannah M Knochelmann, +2 authors, David M Neskey.
Trends Cancer, 2019 Apr 10; 5(4). PMID: 30961829    Free PMC article.
Review.
HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas.
Jérôme R Lechien, Géraldine Descamps, +6 authors, Sven Saussez.
Cancers (Basel), 2020 Apr 30; 12(5). PMID: 32344813    Free PMC article.
Review.
The Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: on Subsets and Subsites.
Niels E Wondergem, Irene H Nauta, +2 authors, Rieneke van de Ven.
Curr Oncol Rep, 2020 Jul 01; 22(8). PMID: 32602047    Free PMC article.
Review.
Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma.
Kyriakos Chatzopoulos, Vassiliki Kotoula, +7 authors, Georgios Fountzilas.
Head Neck Pathol, 2019 Nov 22; 14(3). PMID: 31749124    Free PMC article.
APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma.
Daniel L Faden, Fei Ding, +5 authors, Robert L Ferris.
Oral Oncol, 2019 Aug 20; 96. PMID: 31422205    Free PMC article.
MMP2 as an independent prognostic stratifier in oral cavity cancers.
Caroline Hoffmann, Sophie Vacher, +16 authors, Vassili Soumelis.
Oncoimmunology, 2020 Sep 17; 9(1). PMID: 32934875    Free PMC article.
Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis.
Qiaofen Fu, Nan Chen, +9 authors, Gaofeng Li.
Oncoimmunology, 2019 May 31; 8(7). PMID: 31143514    Free PMC article.
Highly Cited. Review.
Why the Outcome of Anti-Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers.
Jing H Wang.
Bioessays, 2020 Aug 09; 42(10). PMID: 32767371    Free PMC article.
Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15+ Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma.
Samantha M Y Chen, Bian Li, +9 authors, Jing H Wang.
Int J Mol Sci, 2020 Sep 13; 21(18). PMID: 32916850    Free PMC article.
The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles.
Helene Hersvik Aarstad, Svein Erik Emblem Moe, +3 authors, Tor Henrik Anderson Tvedt.
Biomedicines, 2020 Oct 18; 8(10). PMID: 33066437    Free PMC article.
The landscape of CD28, CD80, CD86, CTLA4, and ICOS DNA methylation in head and neck squamous cell carcinomas.
Luka de Vos, Ingela Grünwald, +7 authors, Dimo Dietrich.
Epigenetics, 2020 Apr 14; 15(11). PMID: 32281488    Free PMC article.
Systematic Profiling of Immune Risk Model to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.
Xingyu Liu, Jiarui Chen, +7 authors, Conghua Xie.
Front Genet, 2020 Nov 17; 11. PMID: 33193693    Free PMC article.
An increase of CD8+ T cell infiltration following recurrence is a good prognosticator in HNSCC.
Yoon Kyoung So, Sun-Ju Byeon, +4 authors, Man Ki Chung.
Sci Rep, 2020 Nov 20; 10(1). PMID: 33208791    Free PMC article.
Current progress in the inflammatory background of angiogenesis in gynecological cancers.
Grzegorz Szewczyk, Tomasz M Maciejewski, Dariusz Szukiewicz.
Inflamm Res, 2019 Jan 27; 68(4). PMID: 30680411    Free PMC article.
Review.
Activation of T helper cells in sentinel node predicts poor prognosis in oral squamous cell carcinoma.
Åsa Kågedal, Eric Hjalmarsson, +7 authors, Lars Olaf Cardell.
Sci Rep, 2020 Dec 20; 10(1). PMID: 33339891    Free PMC article.
The prognostic role of prognostic nutritional index in nasopharyngeal carcinoma: A systematic review and meta-analysis.
Min Tang, Zhongxiong Jia, Ju Zhang.
Int J Clin Oncol, 2020 Oct 09; 26(1). PMID: 33029749
Systematic Review.
Epigenetic modulation of immunotherapy and implications in head and neck cancer.
Liye Zhou, Na Xu, +2 authors, Ravindra Uppaluri.
Cancer Metastasis Rev, 2021 Jan 07; 40(1). PMID: 33403469    Free PMC article.
Review.
Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy.
Ajaz A Bhat, Parvaiz Yousuf, +9 authors, Muzafar A Macha.
Signal Transduct Target Ther, 2021 Jan 14; 6(1). PMID: 33436555    Free PMC article.
Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo.
Hamed Mahdikia, Fariba Saadati, +4 authors, Sander Bekeschus.
Oncoimmunology, 2021 Jan 19; 10(1). PMID: 33457077    Free PMC article.
Recent Advances and Future Directions in Clinical Management of Head and Neck Squamous Cell Carcinoma.
Jameel Muzaffar, Shahla Bari, Kedar Kirtane, Christine H Chung.
Cancers (Basel), 2021 Jan 23; 13(2). PMID: 33477635    Free PMC article.
Review.
Immunologic "Cold" Squamous Cell Carcinomas of the Head and Neck Are Associated With an Unfavorable Prognosis.
Julika Ribbat-Idel, Sven Perner, +8 authors, Christian Idel.
Front Med (Lausanne), 2021 Feb 16; 8. PMID: 33585526    Free PMC article.
B-cell clusters at the invasive margin associate with longer survival in early-stage oral-tongue cancer patients.
C Phanthunane, R Wijers, +8 authors, R Debets.
Oncoimmunology, 2021 Mar 02; 10(1). PMID: 33643695    Free PMC article.
PRF1 is a prognostic marker and correlated with immune infiltration in head and neck squamous cell carcinoma.
Cui Fan, Haixia Hu, +4 authors, Mingliang Xiang.
Transl Oncol, 2021 Feb 23; 14(4). PMID: 33618069    Free PMC article.
Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer.
Cristina Valero, Daniella K Zanoni, +7 authors, Snehal G Patel.
Cancer, 2019 Dec 07; 126(5). PMID: 31809562    Free PMC article.
A Novel Syngeneic Immunocompetent Mouse Model of Head and Neck Cancer Pain Independent of Interleukin-1 Signaling.
Matthew J Heussner, Joseph K Folger, +4 authors, Geoffroy Laumet.
Anesth Analg, 2020 Dec 17; 132(4). PMID: 33323783    Free PMC article.
An immune-related seven-lncRNA signature for head and neck squamous cell carcinoma.
Yue Chen, Tian-Qi Luo, +4 authors, Yan-Ping Mao.
Cancer Med, 2021 Mar 05; 10(7). PMID: 33660378    Free PMC article.
Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma.
Charles R Schutt, Hua Sun, +6 authors, Brian A Van Tine.
Oncotarget, 2021 Apr 03; 12(6). PMID: 33796222    Free PMC article.
Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma.
Florencia Veigas, Yamil D Mahmoud, +3 authors, María Romina Girotti.
Cancers (Basel), 2021 Apr 04; 13(5). PMID: 33804419    Free PMC article.
Review.
Epithelial Mutant p53 Promotes Resistance to Anti-PD-1-Mediated Oral Cancer Immunoprevention in Carcinogen-Induced Mouse Models.
Jin Wang, Yuan Hu, +6 authors, Carlos Caulin.
Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33806894    Free PMC article.
Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives.
Stijn J De Keukeleire, Tijl Vermassen, +3 authors, Sylvie Rottey.
Cancers (Basel), 2021 May 01; 13(7). PMID: 33916646    Free PMC article.
Review.
Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis.
Hana Yamaguchi, Miki Hiroi, +5 authors, Yoshihiro Ohmori.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33921389    Free PMC article.
The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.
Natarajan Bhaskaran, Sangeetha Jayaraman, +6 authors, Pushpa Pandiyan.
Front Oncol, 2021 May 11; 11. PMID: 33968777    Free PMC article.
Immune Cell Infiltrates and Neutrophil-to-Lymphocyte Ratio in Relation to Response to Chemotherapy and Prognosis in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas.
Mario Sánchez-Canteli, Luis Juesas, +6 authors, Juan P Rodrigo.
Cancers (Basel), 2021 May 01; 13(9). PMID: 33923066    Free PMC article.
Prognostic significance of tumor-infiltrating lymphocytes and macrophages in nasopharyngeal carcinoma: a systematic review and meta-analysis.
Weixing Liu, Gui Chen, +6 authors, Xiaowen Zhang.
Eur Arch Otorhinolaryngol, 2021 May 25;. PMID: 34027599
Review.
Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
Juan P Rodrigo, Mario Sánchez-Canteli, +7 authors, Alfio Ferlito.
Biomedicines, 2021 May 01; 9(5). PMID: 33925205    Free PMC article.
Review.
Tumor innervation: peripheral nerves take control of the tumor microenvironment.
Stefan M Gysler, Ronny Drapkin.
J Clin Invest, 2021 Jun 02; 131(11). PMID: 34060481    Free PMC article.
Review.
Prognostic Potential of Tumor-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma.
Ana Caruntu, Liliana Moraru, +7 authors, Sabina Zurac.
Cancers (Basel), 2021 Jun 03; 13(9). PMID: 34066837    Free PMC article.
Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma.
Teresa Magnes, Sandro Wagner, +4 authors, Thomas Melchardt.
Int J Mol Sci, 2021 Jun 03; 22(9). PMID: 34067112    Free PMC article.
Review.
AKT3 is a key regulator of head and neck squamous cell carcinoma.
Hideyuki Takahashi, Susumu Rokudai, +4 authors, Kazuaki Chikamatsu.
Cancer Sci, 2021 Apr 04; 112(6). PMID: 33811778    Free PMC article.
Prognostic Relevance of CD4+, CD8+ and FOXP3+ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers.
Paloma Lequerica-Fernández, Julián Suárez-Canto, +6 authors, Juan Carlos de Vicente.
Biomedicines, 2021 Jul 03; 9(6). PMID: 34201050    Free PMC article.
Explant Modeling of the Immune Environment of Head and Neck Cancer.
Shay Sharon, Thomas Duhen, +9 authors, Michael Gough.
Front Oncol, 2021 Jul 06; 11. PMID: 34221953    Free PMC article.
The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis.
Jens M Debacker, Odrade Gondry, +2 authors, Wouter Huvenne.
Cancers (Basel), 2021 Jul 25; 13(14). PMID: 34298638    Free PMC article.
Review.
Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis.
Birhanu Aberha Berele, Yuxiang Cai, Guifang Yang.
Technol Cancer Res Treat, 2021 Jul 30; 20. PMID: 34323154    Free PMC article.
Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma.
Ikko Mito, Hideyuki Takahashi, +3 authors, Kazuaki Chikamatsu.
Sci Rep, 2021 Aug 11; 11(1). PMID: 34373557    Free PMC article.
The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients.
Zuzana Strizova, Martin Snajdauf, +6 authors, Daniel Smrz.
J Cancer Res Clin Oncol, 2020 May 25; 146(8). PMID: 32447483
The Relationship between Tumor-infiltrating Lymphocytes (TILs) and Nasopharyngeal Carcinoma (NPC): A Systematic Review.
Awal Prasetyo, Jethro Budiman, Udadi Sadhana.
Iran J Otorhinolaryngol, 2021 Aug 17; 33(117). PMID: 34395318    Free PMC article.
The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis.
T Müller, M Demes, +4 authors, R Winkelmann.
Clin Transl Oncol, 2021 Aug 28;. PMID: 34449004
Translational Insights and New Therapeutic Perspectives in Head and Neck Tumors.
Morena Fasano, Francesco Perri, +6 authors, Raffaele Solla.
Biomedicines, 2021 Aug 28; 9(8). PMID: 34440249    Free PMC article.
Review.
A 14-Marker Multiplexed Imaging Panel for Prognostic Biomarkers and Tumor Heterogeneity in Head and Neck Squamous Cell Carcinoma.
Junichi Mitsuda, Takahiro Tsujikawa, +9 authors, Shigeru Hirano.
Front Oncol, 2021 Sep 08; 11. PMID: 34490110    Free PMC article.
A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma.
Congyu Shi, Shan Liu, +2 authors, Pan Gao.
BMC Cancer, 2021 Sep 18; 21(1). PMID: 34530752    Free PMC article.
Peripheral blood values as predictors of autoimmune status in oral cavity squamous cell carcinoma.
Anjali Pillai, Cristina Valero, +2 authors, Snehal G Patel.
Transl Oncol, 2021 Sep 15; 14(12). PMID: 34521033    Free PMC article.
Identification of a Novel Signature Predicting Overall Survival in Head and Neck Squamous Cell Carcinoma.
Haige Zheng, Huixian Liu, Yumin Lu, Hengguo Li.
Front Surg, 2021 Oct 12; 8. PMID: 34631779    Free PMC article.
[Effects of neoadjuvant chemoradiotherapy on infiltrating immune cells in the tumor microenvironment of rectal cancer].
Q Yang, C Zhou, +4 authors, J Ma.
Nan Fang Yi Ke Da Xue Xue Bao, 2021 Sep 23; 41(8). PMID: 34549721    Free PMC article.
Assessment of Immune Cell Populations in Tumor Tissue and Peripheral Blood Samples from Head and Neck Squamous Cell Carcinoma Patients.
Ana Caruntu, Liliana Moraru, +6 authors, Monica Neagu.
Anal Cell Pathol (Amst), 2021 Oct 26; 2021. PMID: 34692375    Free PMC article.
Development and Characterization of a Novel Non-Lytic Cancer Immunotherapy Using a Recombinant Arenavirus Vector Platform.
Henning Lauterbach, Sarah Schmidt, +12 authors, Klaus K Orlinger.
Front Oncol, 2021 Nov 02; 11. PMID: 34722273    Free PMC article.
Review.
The Immune Infiltration in HNSCC and Its Clinical Value: A Comprehensive Study Based on the TCGA and GEO Databases.
Xizhe Sun, Lijia Zhang, Songjiang Liu.
Comput Math Methods Med, 2021 Nov 19; 2021. PMID: 34790249    Free PMC article.