Journal Article
. 2014 Oct; 51(1):90-5.
doi: 10.1016/j.oraloncology.2014.09.006.

Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study

Gregory T Wolf 1 Douglas B Chepeha 2 Emily Bellile 3 Ariane Nguyen 2 Daffyd Thomas 4 Jonathan McHugh 4 University of Michigan Head and Neck SPORE Program  
  • PMID: 25283344
  •     52 References
  •     58 citations


Objectives: Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined.

Methods: Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months.

Results: The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion.

Conclusion: Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma.

Keywords: Oral cavity cancer; Tumor associated macrophage; Tumor infiltrating lymphocytes.

CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans.
Rong Rong Huang, Jason Jalil, +10 authors, Antoni Ribas.
Clin Cancer Res, 2011 May 12; 17(12). PMID: 21558401    Free PMC article.
CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.
Gregory L Beatty, Elena G Chiorean, +10 authors, Robert H Vonderheide.
Science, 2011 Mar 26; 331(6024). PMID: 21436454    Free PMC article.
Highly Cited.
Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins.
C L Holness, D L Simmons.
Blood, 1993 Mar 15; 81(6). PMID: 7680921
Highly Cited.
Current experience with CTLA4-blocking monoclonal antibodies for the treatment of solid tumors.
Sanjiv S Agarwala, Antoni Ribas.
J Immunother, 2010 Jun 17; 33(6). PMID: 20551840
A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth.
Binzhi Qian, Yan Deng, +5 authors, Jeffrey W Pollard.
PLoS One, 2009 Aug 12; 4(8). PMID: 19668347    Free PMC article.
Highly Cited.
The tumor microenvironment and its role in promoting tumor growth.
T L Whiteside.
Oncogene, 2008 Oct 07; 27(45). PMID: 18836471    Free PMC article.
Highly Cited. Review.
Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice.
Jinlin Liu, Ning Zhang, +6 authors, Honglin Wang.
PLoS One, 2011 May 12; 6(4). PMID: 21559338    Free PMC article.
Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy.
Sylvain Ladoire, Laurent Arnould, +9 authors, François Ghiringhelli.
Breast Cancer Res Treat, 2010 Mar 17; 125(1). PMID: 20229175
Interleukin-6 predicts recurrence and survival among head and neck cancer patients.
Sonia A Duffy, Jeremy M G Taylor, +5 authors, Theodoros N Teknos.
Cancer, 2008 Jun 07; 113(4). PMID: 18536030
Highly Cited.
Number of CD4+ cells and location of forkhead box protein P3-positive cells in diagnostic follicular lymphoma tissue microarrays correlates with outcome.
Abigail M Lee, Andrew J Clear, +8 authors, Lindsey K Goff.
J Clin Oncol, 2006 Oct 13; 24(31). PMID: 17033038
Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies.
Cécile Badoual, Federico Sandoval, +9 authors, Eric Tartour.
Head Neck, 2010 Mar 02; 32(7). PMID: 20191626
Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer.
Patrick J Schuler, Malgorzata Harasymczuk, +5 authors, Theresa L Whiteside.
Clin Cancer Res, 2013 Oct 08; 19(23). PMID: 24097865    Free PMC article.
Prognostic and predictive impact of intra- and peritumoral immune infiltrates.
Wolf Herman Fridman, Jérôme Galon, +3 authors, Guido Kroemer.
Cancer Res, 2011 Aug 19; 71(17). PMID: 21846822
Highly Cited. Review.
Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis.
Kai-Ping Chang, Huang-Kai Kao, +9 authors, Jau-Song Yu.
Oral Oncol, 2010 Dec 18; 47(2). PMID: 21163685
Macrophage diversity enhances tumor progression and metastasis.
Bin-Zhi Qian, Jeffrey W Pollard.
Cell, 2010 Apr 08; 141(1). PMID: 20371344    Free PMC article.
Highly Cited. Review.
The frequency and suppressor function of CD4+CD25highFoxp3+ T cells in the circulation of patients with squamous cell carcinoma of the head and neck.
Laura Strauss, Christoph Bergmann, +2 authors, Theresa L Whiteside.
Clin Cancer Res, 2007 Nov 03; 13(21). PMID: 17975141
Highly Cited.
Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer.
Derrick Wansom, Emily Light, +13 authors, Gregory T Wolf.
Arch Otolaryngol Head Neck Surg, 2010 Dec 22; 136(12). PMID: 21173378    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.
Increased prevalence of interleukin-17-producing CD4(+) tumor infiltrating lymphocytes in human oral squamous cell carcinoma.
Jang-Jaer Lee, Yen-Liang Chang, +6 authors, Jean-San Chia.
Head Neck, 2011 Aug 13; 33(9). PMID: 21837700
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target.
Sandra D Bohling, Kimberly H Allison.
Mod Pathol, 2008 Sep 30; 21(12). PMID: 18820666
Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck.
Kazuaki Chikamatsu, Koichi Sakakura, Theresa L Whiteside, Nobuhiko Furuya.
Head Neck, 2006 Nov 15; 29(2). PMID: 17103408
Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.
Carsten Denkert, Sibylle Loibl, +14 authors, Gunter von Minckwitz.
J Clin Oncol, 2009 Nov 18; 28(1). PMID: 19917869
Highly Cited.
Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner.
Peiwen Chen, Yujie Huang, +5 authors, Yongzhang Luo.
Clin Cancer Res, 2011 Oct 14; 17(23). PMID: 21994414
Predictors of locoregional recurrence in early stage oral cavity cancer with free surgical margins.
Tsai-Ying Huang, Lee-Ping Hsu, +6 authors, Peir-Rong Chen.
Oral Oncol, 2009 Dec 17; 46(1). PMID: 20005769
Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.
G T Wolf, T E Carey.
J Natl Cancer Inst Monogr, 1992 Jan 01; (13). PMID: 1389697
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.
Targeting regulatory T cells in cancer.
William L Byrne, Kingston H G Mills, James A Lederer, Gerald C O'Sullivan.
Cancer Res, 2011 Nov 10; 71(22). PMID: 22068034    Free PMC article.
FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy.
Hazem Ghebeh, Eman Barhoush, +3 authors, Said Dermime.
BMC Cancer, 2008 Feb 26; 8. PMID: 18294387    Free PMC article.
In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.
Sylvain Ladoire, Grégoire Mignot, +11 authors, François Ghiringhelli.
J Pathol, 2011 Mar 26; 224(3). PMID: 21437909
Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers.
Cécile Badoual, Stéphane Hans, +9 authors, Eric Tartour.
Clin Cancer Res, 2006 Jan 24; 12(2). PMID: 16428488
Highly Cited.
Tissue microarrays (TMAs) for high-throughput molecular pathology research.
A Nocito, J Kononen, O P Kallioniemi, G Sauter.
Int J Cancer, 2001 Oct 23; 94(1). PMID: 11668471
Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.
David G DeNardo, Donal J Brennan, +12 authors, Lisa M Coussens.
Cancer Discov, 2011 Nov 01; 1(1). PMID: 22039576    Free PMC article.
Highly Cited.
Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma.
Benjamin Marcus, Douglas Arenberg, +10 authors, Theodoros N Teknos.
Cancer, 2004 Nov 17; 101(12). PMID: 15546137
Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma.
S A Goldman, E Baker, +3 authors, M T Lotze.
Arch Otolaryngol Head Neck Surg, 1998 Jun 25; 124(6). PMID: 9639473
Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia.
Matthias Haas, Arno Dimmler, +3 authors, Luitpold V Distel.
BMC Gastroenterol, 2009 Sep 08; 9. PMID: 19732435    Free PMC article.
Clinical significance of langerhans cells in squamous cell carcinoma of the larynx.
Francisco Esteban, Francisco Ruiz-Cabello, +3 authors, Maximino Redondo.
J Oncol, 2012 Apr 07; 2012. PMID: 22481933    Free PMC article.
Langerhans cells and T cells sense cell dysplasia in oral leukoplakias and oral squamous cell carcinomas--evidence for immunosurveillance.
J Öhman, B Magnusson, +2 authors, B Hasséus.
Scand J Immunol, 2012 Apr 04; 76(1). PMID: 22469080
Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer.
Sahar M A Mahmoud, Emma Claire Paish, +5 authors, Andrew R Green.
J Clin Oncol, 2011 Apr 13; 29(15). PMID: 21483002
Highly Cited.
A unique subset of CD4+CD25highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment.
Laura Strauss, Christoph Bergmann, +3 authors, Theresa L Whiteside.
Clin Cancer Res, 2007 Aug 03; 13(15 Pt 1). PMID: 17671115
Highly Cited.
Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.
Michael J Campbell, Nathan Y Tonlaar, +14 authors, Laura J Esserman.
Breast Cancer Res Treat, 2010 Sep 16; 128(3). PMID: 20842526    Free PMC article.
Highly Cited.
Oral cancer treatment and immune targets - a role for dendritic cells?
Hans-Robert Metelmann, Peter Hyckel, Fred Podmelle.
J Craniomaxillofac Surg, 2011 Apr 05; 40(2). PMID: 21459014
Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors.
Anne-Katrine Bonde, Verena Tischler, +2 authors, Reto A Schwendener.
BMC Cancer, 2012 Jan 26; 12. PMID: 22273460    Free PMC article.
Highly Cited.
Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.
C Schaefer, G G Kim, +3 authors, T L Whiteside.
Br J Cancer, 2005 Feb 17; 92(5). PMID: 15714205    Free PMC article.
[The "classical" macrophage marker CD68 is strongly expressed in primary human fibroblasts].
L A Kunz-Schughart, A Weber, +5 authors, M Kreutz.
Verh Dtsch Ges Pathol, 2006 Aug 08; 87. PMID: 16888915
Macrophages, innate immunity and cancer: balance, tolerance, and diversity.
Alberto Mantovani, Antonio Sica.
Curr Opin Immunol, 2010 Feb 11; 22(2). PMID: 20144856
Highly Cited. Review.
Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy.
Niels Halama, Sara Michel, +16 authors, Dirk Jaeger.
Cancer Res, 2011 Aug 19; 71(17). PMID: 21846824
Highly Cited.
Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis.
G T Wolf, J L Hudson, +2 authors, K D McClatchey.
Otolaryngol Head Neck Surg, 1986 Sep 01; 95(2). PMID: 2954014
Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer.
Sylvain Ladoire, François Martin, François Ghiringhelli.
Cancer Immunol Immunother, 2011 Jun 07; 60(7). PMID: 21644034
Highly Cited. Review.
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
The number of intratumoral dendritic cells and zeta-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma.
T E Reichert, C Scheuer, +2 authors, T L Whiteside.
Cancer, 2001 Jun 08; 91(11). PMID: 11391595
Trial watch: Dendritic cell-based interventions for cancer therapy.
Erika Vacchelli, Ilio Vitale, +8 authors, Lorenzo Galluzzi.
Oncoimmunology, 2013 Nov 29; 2(10). PMID: 24286020    Free PMC article.
Immunophenotyping of patients with oral squamous cell carcinoma in peripheral blood and associated tumor tissue.
Martin Grimm, Oliver Feyen, +4 authors, Siegmar Reinert.
Tumour Biol, 2015 Oct 18; 37(3). PMID: 26474587
Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches.
Clint T Allen, Paul E Clavijo, Carter Van Waes, Zhong Chen.
Cancers (Basel), 2015 Dec 23; 7(4). PMID: 26690220    Free PMC article.
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.
Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer.
Ruth J Davis, Carter Van Waes, Clint T Allen.
Oral Oncol, 2016 May 25; 58. PMID: 27215705    Free PMC article.
Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer.
Yu Lei, Yuying Xie, +4 authors, Gregory T Wolf.
Oral Oncol, 2016 Aug 25; 61. PMID: 27553942    Free PMC article.
Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles.
Rodney Macedo, Juliette Rochefort, +11 authors, François M Lemoine.
Oncoimmunology, 2016 Sep 14; 5(7). PMID: 27622018    Free PMC article.
Prognostic Value of Tumor-Infiltrating Lymphocytes for Patients With Head and Neck Squamous Cell Carcinoma.
Qiaoshi Xu, Chong Wang, +2 authors, Zhengxue Han.
Transl Oncol, 2016 Nov 27; 10(1). PMID: 27888708    Free PMC article.
TILs in Head and Neck Cancer: Ready for Clinical Implementation and Why (Not)?
Astrid De Meulenaere, Tijl Vermassen, +3 authors, Liesbeth Ferdinande.
Head Neck Pathol, 2016 Dec 30; 11(3). PMID: 28032290    Free PMC article.
Differentiated State of Initiating Tumor Cells Is Key to Distinctive Immune Responses Seen in H-RasG12V-Induced Squamous Tumors.
Michael A Podolsky, Jacob T Bailey, +3 authors, Adam B Glick.
Cancer Immunol Res, 2017 Feb 01; 5(3). PMID: 28137717    Free PMC article.
Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.
Richard Linedale, Campbell Schmidt, +4 authors, Graham R Leggatt.
PLoS One, 2017 Apr 20; 12(4). PMID: 28423034    Free PMC article.
HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer.
Tristan A Barnes, Eitan Amir.
Br J Cancer, 2017 Jul 14; 117(4). PMID: 28704840    Free PMC article.
Highly Cited. Review.
T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma.
Daniele Maggioni, Lorenzo Pignataro, Werner Garavello.
Oncoimmunology, 2017 Aug 16; 6(7). PMID: 28811959    Free PMC article.
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, Marc L Ooft, Lot A Devriese, Stefan M Willems.
Oncoimmunology, 2017 Nov 18; 6(11). PMID: 29147608    Free PMC article.
Highly Cited. Review.
Prognostic value of CD45 transcriptional expression in head and neck cancer.
Mercedes Camacho, Adriana Agüero, +6 authors, Xavier León.
Eur Arch Otorhinolaryngol, 2017 Nov 28; 275(1). PMID: 29177949
Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma.
Rebecca Hoesli, Andrew C Birkeland, +12 authors, Matthew E Spector.
Oral Oncol, 2018 Jan 25; 77. PMID: 29362129    Free PMC article.
The role of macrophages and eosinophils in reactive lesions of the oral cavity.
Amir Ala Aghbali, Ayshin Akbarzadeh, Maryam Kouhsoltani.
J Oral Maxillofac Pathol, 2018 May 08; 22(1). PMID: 29731578    Free PMC article.
CD20+ Tumor Infiltrating B Lymphocyte in Oral Squamous Cell Carcinoma: Correlation with Clinicopathologic Characteristics and Heat Shock Protein 70 Expression.
Nasim Taghavi, Zhaleh Mohsenifar, Alireza Akbarzadeh Baghban, Alireza Arjomandkhah.
Patholog Res Int, 2018 Jun 01; 2018. PMID: 29850009    Free PMC article.
A Comparative Study of Macrophage Density in Odontogenic Cysts and Tumors with Diverse Clinical Behavior.
Maryam Kouhsoltani, Mahsa Abdolhosseinzadeh, +3 authors, Tala Pourlak.
J Dent (Shiraz), 2018 Jun 02; 19(2). PMID: 29854889    Free PMC article.
Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples.
Kevin B Givechian, Kamil Wnuk, +5 authors, Patrick Soon-Shiong.
NPJ Genom Med, 2018 Jun 22; 3. PMID: 29928512    Free PMC article.
Prognostic significance of tumor-infiltrating lymphocytes in patients with operable tongue cancer.
Wan-Yu Chen, Chen-Tu Wu, +6 authors, Ann-Lii Cheng.
Radiat Oncol, 2018 Aug 30; 13(1). PMID: 30153850    Free PMC article.
Predictive biomarkers for tumor immune checkpoint blockade.
Mengting Tong, Jing Wang, +4 authors, Hongliang Zhang.
Cancer Manag Res, 2018 Oct 24; 10. PMID: 30349382    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.
Deciphering the Role of Regulatory CD4 T Cells in Oral and Oropharyngeal Cancer: A Systematic Review.
Caoimhín O'Higgins, Frank J Ward, Rasha Abu Eid.
Front Oncol, 2018 Nov 22; 8. PMID: 30460193    Free PMC article.
Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck.
Gregory T Wolf, William Winter, +8 authors, Head and Neck SPORE Program.
Oral Oncol, 2018 Dec 12; 87. PMID: 30527240    Free PMC article.
Antitumor properties of triptolide: phenotype regulation of macrophage differentiation.
Han Li, Liping Li, +7 authors, Lixin Sun.
Cancer Biol Ther, 2019 Oct 31; 21(2). PMID: 31663424    Free PMC article.
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.
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.
Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares.
Yuning Hao, Ming Yan, +2 authors, Yuying Xie.
PLoS Comput Biol, 2019 May 07; 15(5). PMID: 31059559    Free PMC article.
Periodontitis and oral cancer - current concepts of the etiopathogenesis.
Soussan Irani, Iman Barati, Mohammadreza Badiei.
Oncol Rev, 2020 Apr 02; 14(1). PMID: 32231765    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.
Prognostic significance of systemic immune-inflammation index in patients with intrahepatic cholangiocarcinoma undergoing hepatic resection.
Hui Li, Jin-Ju Wang, +4 authors, Hong Wu.
World J Gastrointest Oncol, 2020 May 06; 12(4). PMID: 32368324    Free PMC article.
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.
Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer.
Danian Dai, Bo Chen, +4 authors, Jihong Liu.
Aging (Albany NY), 2020 May 29; 12(10). PMID: 32463792    Free PMC article.
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.
The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma.
Jie Wang, Shu Tian, +3 authors, Chunyan Hu.
BMC Cancer, 2020 Aug 08; 20(1). PMID: 32758195    Free PMC article.
Heterogeneity of the Head and Neck Squamous Cell Carcinoma Immune Landscape and Its Impact on Immunotherapy.
Madison Canning, Gang Guo, +4 authors, Yan Cui.
Front Cell Dev Biol, 2019 Apr 27; 7. PMID: 31024913    Free PMC article.
Highly Cited. Review.
Immune reaction by cytoreductive prostatectomy.
Geun Taek Lee, Arnav Srivastava, Young Suk Kwon, Isaac Yi Kim.
Am J Clin Exp Urol, 2019 May 30; 7(2). PMID: 31139701    Free PMC article.
Computer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray.
Sangjune Laurence Lee, Michael Cabanero, +12 authors, Scott V Bratman.
Clin Transl Radiat Oncol, 2019 Jun 14; 17. PMID: 31193592    Free PMC article.
CXCL12 is associated with FoxP3+ tumor-infiltrating lymphocytes and affects the survival of patients with oral squamous cell carcinoma.
Bowen Zhang, Chenzhou Wu, +4 authors, Longjiang Li.
Oncol Lett, 2019 Aug 20; 18(2). PMID: 31423170    Free PMC article.
Digital Image Analysis of CD8+ and CD3+ Tumor-Infiltrating Lymphocytes in Tongue Squamous Cell Carcinoma.
Yenlin Huang, Chieh Lin, +5 authors, Kai-Ping Chang.
Cancer Manag Res, 2020 Sep 29; 12. PMID: 32982423    Free PMC article.
Unanswered Questions on the Optimal Extent of Tongue Cancer Resections.
Bipin T Varghese.
Indian J Surg Oncol, 2020 Oct 23; 11(Suppl 1). PMID: 33088131    Free PMC article.
Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma.
Barbara Seliger, Chiara Massa, +4 authors, Claudia Wickenhauser.
Int J Mol Sci, 2020 Sep 30; 21(19). PMID: 32987799    Free PMC article.
Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma.
Jacqueline E Mann, Joshua D Smith, +16 authors, J Chad Brenner.
Cancer Immunol Immunother, 2018 Oct 27; 68(2). PMID: 30361882    Free PMC article.
A novel integrated platform for the identification of surgical margins in oral squamous cell carcinoma: results from a prospective single-institution series.
Alessandro Baj, Nicola Fusco, +6 authors, Pasquale Capaccio.
BMC Cancer, 2019 May 19; 19(1). PMID: 31101023    Free PMC article.
Assessment of tumor-associated immune cells in laryngeal squamous cell carcinoma.
Liyuan Zhou, Yujun Li, +9 authors, Binquan Wang.
J Cancer Res Clin Oncol, 2019 May 23; 145(7). PMID: 31115672
Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival.
Geetashree Mukherjee, Swarnendu Bag, +7 authors, Suparna Dutt.
PLoS One, 2020 Nov 20; 15(11). PMID: 33211709    Free PMC article.
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.
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.
Chemokine-Cytokine Networks in the Head and Neck Tumor Microenvironment.
Sabah Nisar, Parvaiz Yousuf, +9 authors, Muzafar A Macha.
Int J Mol Sci, 2021 May 01; 22(9). PMID: 33925575    Free PMC article.
High SEC61G expression predicts poor prognosis in patients with Head and Neck Squamous Cell Carcinomas.
Leifeng Liang, Qingwen Huang, +6 authors, Kai Hu.
J Cancer, 2021 Jun 08; 12(13). PMID: 34093796    Free PMC article.
Recent Advances in Head and Neck Tumor Microenvironment-Based Therapy.
Muzafar A Macha, Nissar A Wani, +7 authors, Surinder K Batra.
Adv Exp Med Biol, 2020 Jan 01; 1296. PMID: 34185284
Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response.
Pengfei Diao, Yue Jiang, +17 authors, Jie Cheng.
J Immunother Cancer, 2021 Jun 17; 9(6). PMID: 34130988    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.
Tumor microenvironment is not an 'innocent bystander' in the resistance to treatment of head and neck cancers (Review).
Laura Mazilu, Andra-Iulia Suceveanu, +3 authors, Serban-Mircea Negru.
Exp Ther Med, 2021 Sep 02; 22(4). PMID: 34466142    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.
CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1.
Dan Ai, Yu Dou, +14 authors, Xun Qu.
Front Oncol, 2021 Sep 28; 11. PMID: 34568076    Free PMC article.
High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments.
Łukasz Jan Adamski, Anna Starzyńska, +7 authors, Rafał Pęksa.
Biomedicines, 2021 Sep 29; 9(9). PMID: 34572318    Free PMC article.
A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.
Li Xu, Ying-Ying Li, +4 authors, Zhao-Hui Liu.
Dis Markers, 2021 Dec 03; 2021. PMID: 34853622    Free PMC article.