Review
. 2020 Jan; 68(2):80-86.
doi: 10.1007/s00106-019-00804-0.

[Comparison of T cell response in the tumor milieu of patients with HPV+ and HPV- head and neck cancer]

T Bastian 1 S Lang 1 B A Kansy 2 
Affiliations
  • PMID: 31915881
  •     30 References
  •     1 citations

Abstract

Background: The incidence of HPV-associated squamous cell carcinoma of the head and neck region (HNSCC) has increased dramatically in recent years. Despite a similar localization (oropharyngeal squamous cell epithelia) to smoking- and alcohol-associated cancers, HPV-associated carcinomas are considered to represent a distinct entity. Reasons for the different therapeutic responses of the two tumor entities are not yet fully understood.

Methods And Objective: This review investigates the importance of tumor-infiltrating lymphocytes in HPV+ and HPV- HNSCC by means of articles and publications concerning the tumor micromilieu, effects on prognosis, and patients' therapeutic responses.

Results: HNSCC patients with a positive HPV status and increased frequencies of CD8+ T cells (CD, cluster of differentiation) demonstrated an improved therapeutic response and improved outcomes. Decreased expression of the EGF (epidermal growth factor) receptor correlates with increased TH1 cytokine secretion by CD4+ T cells, which, in their role as T helper cells, can activate macrophages, dendritic cells, and cytotoxic T cells, amongst others. Regulatory T cells (Treg) execute an immune-suppressive effect in the tumor micromilieu through different metabolic and signaling pathways (IL[interleukin]‑4, IL-10, TGF‑β ["transforming growth factor‑β"]).

Conclusion: The importance of the adaptive immune response for treatment response and patients' prognosis has been supported by different investigations. Understanding the immunological processes in the tumor environment plays an important role for the development of new treatment approaches.

Keywords: Human papilloma virus; Immunotherapy; Oropharynx neoplasms; Squamous cell carcinoma; Tumour infiltrating lymphocytes.

Other Links

Full text on HNO
Histoepigenetic analysis of HPV- and tobacco-associated head and neck cancer identifies both subtype-specific and common therapeutic targets despite divergent microenvironments.
Ivenise Carrero, Hsuan-Chen Liu, Andrew G Sikora, Aleksandar Milosavljevic.
Oncogene, 2019 Jan 19; 38(19). PMID: 30655605    Free PMC article.
IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity.
V Shankaran, H Ikeda, +4 authors, R D Schreiber.
Nature, 2001 Apr 27; 410(6832). PMID: 11323675
Highly Cited.
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.
A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell.
J P Ridge, F Di Rosa, P Matzinger.
Nature, 1998 Jun 12; 393(6684). PMID: 9624003
Highly Cited.
Human papillomavirus and rising oropharyngeal cancer incidence in the United States.
Anil K Chaturvedi, Eric A Engels, +15 authors, Maura L Gillison.
J Clin Oncol, 2011 Oct 05; 29(32). PMID: 21969503    Free PMC article.
Highly Cited.
Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas.
J P Klussmann, S J Weissenborn, +7 authors, P G Fuchs.
Cancer, 2001 Dec 26; 92(11). PMID: 11753961
CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.
C Kurts, F R Carbone, +4 authors, J F Miller.
J Exp Med, 1998 Feb 12; 186(12). PMID: 9396776    Free PMC article.
Human papillomavirus and survival of patients with oropharyngeal cancer.
K Kian Ang, Jonathan Harris, +12 authors, Maura L Gillison.
N Engl J Med, 2010 Jun 10; 363(1). PMID: 20530316    Free PMC article.
Highly Cited.
PD-1 Status in CD8+ T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer.
Benjamin A Kansy, Fernando Concha-Benavente, +13 authors, Robert L Ferris.
Cancer Res, 2017 Sep 15; 77(22). PMID: 28904066    Free PMC article.
Highly Cited.
Human Papilloma Virus Specific Immunogenicity and Dysfunction of CD8+ T Cells in Head and Neck Cancer.
Sri Krishna, Peaches Ulrich, +10 authors, Karen S Anderson.
Cancer Res, 2018 Aug 30; 78(21). PMID: 30154146
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.
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.
Tumor-infiltrating lymphocytes favor the response to chemoradiotherapy of head and neck cancer.
Panagiotis Balermpas, Franz Rödel, +2 authors, Emmanouil Fokas.
Oncoimmunology, 2014 Apr 09; 3(1). PMID: 24711959    Free PMC article.
Human papillomavirus tumor-infiltrating T-regulatory lymphocytes and P53 codon 72 polymorphisms correlate with clinical staging and prognosis of oropharyngeal cancer.
Massimo Rittà, Vincenzo Landolfo, +8 authors, Santo Landolfo.
New Microbiol, 2013 May 21; 36(2). PMID: 23686119
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.
CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer.
Liam Masterson, Matt Lechner, +7 authors, Jane Sterling.
Eur J Cancer, 2016 Sep 27; 67. PMID: 27669501
Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.
Shayan Cheraghlou, Phoebe K Yu, +6 authors, Benjamin L Judson.
Cancer, 2017 Dec 16; 124(4). PMID: 29243245
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Jacques Ferlay, Isabelle Soerjomataram, +6 authors, Freddie Bray.
Int J Cancer, 2014 Sep 16; 136(5). PMID: 25220842
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.
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.
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
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.
CD8 lethargy in the absence of CD4 help.
Christine Bourgeois, Henrique Veiga-Fernandes, +2 authors, Corinne Tanchot.
Eur J Immunol, 2002 Sep 05; 32(8). PMID: 12209632
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.
CD8-alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis.
Alain C Jung, Sébastien Guihard, +9 authors, Joseph Abecassis.
Int J Cancer, 2012 Aug 15; 132(2). PMID: 22890882
Intratumoral HPV16-Specific T Cells Constitute a Type I-Oriented Tumor Microenvironment to Improve Survival in HPV16-Driven Oropharyngeal Cancer.
Marij J P Welters, Wenbo Ma, +11 authors, Sjoerd H van der Burg.
Clin Cancer Res, 2017 Oct 12; 24(3). PMID: 29018052
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.
Expression of EGFR and HPV-associated p16 in oropharyngeal carcinoma: correlation and influence on prognosis after radiotherapy in the randomized DAHANCA 5 and 7 trials.
Pernille Lassen, Jens Overgaard, Jesper Grau Eriksen.
Radiother Oncol, 2013 Sep 26; 108(3). PMID: 24060179
Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers.
Ravindra Uppaluri, Gavin P Dunn, James S Lewis.
Cancer Immun, 2008 Dec 05; 8. PMID: 19053167    Free PMC article.
Review.
Consensus nomenclature for CD8+ T cell phenotypes in cancer.
Lionel Apetoh, Mark J Smyth, +56 authors, Ana C Anderson.
Oncoimmunology, 2015 Jul 03; 4(4). PMID: 26137416    Free PMC article.
Highly Cited.
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.