CD8-alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis.
Alain C. Jung,Sébastien Guihard,Sylvie Krugell,Sonia Ledrappier,Alexandra Brochot,Véronique Dalstein,Sylvie Job,Aurélien de Reyniès,Georges Noël,Bohdan Wasylyk,Christine Clavel,Joseph Abecassis +11 more
TLDR
The results suggest that an increased cytotoxic T‐cell‐based antitumor immune response is involved in improved prognosis of patients with HPV‐positive tumors.Abstract:
Patients with human papillomavirus (HPV)-related oropharyngeal tumors display improved prognosis. The biological basis of this tumor phenotype is poorly understood. We investigated whether increased lymphocyte infiltrate in HPV-positive oropharyngeal squamous cell carcinomas could account for better prognosis. We previously identified, in an Affymetrix GeneChip analysis of 83 HPV-unrelated and 11 HPV-related squamous cell carcinoma of the oropharynx, several candidate genes, including CD8α and CD3ζ. Their expression was validated in this study by qRT–PCR on an independent clinical series of 144 oropharyngeal tumors. Immunohistochemical staining of tumor specimens was performed to evaluate infiltration of tumor stroma by CD8+ and CD4+ lymphocytes. The prognostic value of CD8α and CD3ζ expression levels was measured by Kaplan–Meier and Cox regression model analyses. Immune response-related signaling pathways were found to be deregulated in HPV-positive oropharyngeal tumors. Expression of CD8α, CD3ζ, granzyme K, CD28 and integrin αL RNAs was upregulated in HPV-positive lesions when compared with HPV-unrelated tumors (p < 0.05). Stroma of HPV-positive tumors was frequently and strongly infiltrated by CD8α- and CD3ζ-positive T cells. CD8α RNA expression correlated with both improved global (Kaplan–Meier; p = 0.005; Cox regression: p = 0.003) and disease-free (Cox regression: p = 0.04) survival. CD3ζ RNA expression correlated with improved overall survival (Cox regression: p = 0.024). These results suggest that an increased cytotoxic T-cell-based antitumor immune response is involved in improved prognosis of patients with HPV-positive tumors.read more
Citations
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Journal ArticleDOI
Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents.
TL;DR: The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy.
Journal ArticleDOI
Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma.
Nghia Pham Trung Nguyen,Emily Bellile,Daffyd Thomas,Jonathan B. McHugh,Laura S. Rozek,Shama Virani,Lisa A. Peterson,Thomas E. Carey,Heather M. Walline,Jeffery Moyer,Matthew E. Spector,Daniel Perim,Mark E. Prince,Scott G. McLean,Carol R. Bradford,Jeremy M. G. Taylor,Gregory T. Wolf +16 more
TL;DR: Because immune responses within the tumor microenvironment are important predictors of tumor biology, correlations of types of tumor infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients with head and neck squamous cell carcinoma.
Journal ArticleDOI
CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG)
Panagiotis Balermpas,Panagiotis Balermpas,Franz Rödel,Franz Rödel,Claus Rödel,Claus Rödel,Mechthild Krause,Annett Linge,Annett Linge,Fabian Lohaus,Fabian Lohaus,Michael Baumann,Inge Tinhofer,Inge Tinhofer,Volker Budach,Volker Budach,Eleni Gkika,Eleni Gkika,Martin Stuschke,Martin Stuschke,Melanie Avlar,Melanie Avlar,Anca Lidia Grosu,Anca Lidia Grosu,Amir Abdollahi,Jürgen Debus,Christine Bayer,Stefan Stangl,Claus Belka,Claus Belka,Steffi Pigorsch,Steffi Pigorsch,Gabriele Multhoff,Gabriele Multhoff,Stephanie E. Combs,Stephanie E. Combs,David Mönnich,David Mönnich,Daniel Zips,Daniel Zips,Emmanouil Fokas,Emmanouil Fokas +41 more
TL;DR: It is indicated that CD8‐positive TILs have antitumour activity and could be used for treatment stratification and its role in the immune response in SCCHN patients after adjuvant chemoradiotherapy is warranted and will be performed in the prospective DKTK‐ROG study.
Book ChapterDOI
Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers.
Etienne Becht,Nicolas A. Giraldo,Claire Germain,Aurélien de Reyniès,Pierre Laurent-Puig,Jessica Zucman-Rossi,Marie-Caroline Dieu-Nosjean,Catherine Sautès-Fridman,Wolf H. Fridman +8 more
TL;DR: The description and the understanding of the immune and inflammatory landscape in human tumors are of paramount importance and completes the mutational, transcriptional, and epigenetic patterns of the malignant cells and open paths to understand how tumor cells shape their immune microenvironment and are shaped by the immune reaction.
Journal ArticleDOI
Increased radiosensitivity of HPV-positive head and neck cancers: Molecular basis and therapeutic perspectives
TL;DR: Current evidence on the biological basis of increased radiosensitivity in HPV-positive HNSCC is reviewed and potential therapeutic implications are discussed.
References
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BookDOI
TNM classification of malignant tumours
TL;DR: Head and Neck Tumours.- Lip and Oral Cavity.- Pharynx.- Larynx.' Maxillary Sinus.- Salivary Glands.- Thyroid Gland.- Digestive System Tumour .
Journal ArticleDOI
Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
K. Kian Ang,Jonathan Harris,Richard H. Wheeler,Randal S. Weber,David I. Rosenthal,Phuc Felix Nguyen-Tân,William H. Westra,Christine H. Chung,Richard C.K. Jordan,Charles Lu,Harold Kim,Rita Axelrod,C Craig Silverman,Kevin P. Redmond,Maura L. Gillison +14 more
TL;DR: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer and the risk of death significantly increased with each additional pack-year of tobacco smoking.
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Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
TL;DR: A unifying conceptual framework called “cancer immunoediting,” which integrates the immune system’s dual host-protective and tumor-promoting roles is discussed.
Journal ArticleDOI
Case-control study of human papillomavirus and oropharyngeal cancer.
Aimée R. Kreimer,Raphael P. Viscidi,Michael Pawlita,Carole Fakhry,Wayne M. Koch,William H. Westra,Maura L. Gillison +6 more
TL;DR: Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection, and the degree of association increased with the number of vaginal-sex and oral-sex partners, among subjects with or without the established risk factors of tobacco and alcohol use.
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