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)

Balermpas, Panagiotis; Rödel, Franz; Rödel, Claus; Krause, Mechthild; Linge, Annett; Lohaus, Fabian; Baumann, Michaël; Tinhofer, Ingeborg; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Avlar, Melanie; Grosu, Anca L.; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Stangl, Stefan; Belka, Claus; Pigorsch, Steffi; Multhoff, Gabriele; Combs, Stephanie E.; Mönnich, David; Zips, Daniel; Fokas, Emmanouil

doi:10.1002/ijc.29683

Cited by 176 publications

(183 citation statements)

References 48 publications

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“…PD-L1 positivity was defined as PD-L1 expression on ≥5% of all TC or IC based on immunohistochemistry. The densities of TILs were semi-quantitatively scored by measuring CD3 + and CD8 + T cells based on previously used methods232425. The abundance of TILs infiltrating tumor cell nests was evaluated by examining five representative high-power fields under 400x magnifications.…”

Section: Methodsmentioning

confidence: 99%

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

Kim

Hong

et al. 2016

Sci Rep

221

169

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To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.

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Section: Methodsmentioning

confidence: 99%

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

Kim

Hong

et al. 2016

Sci Rep

221

169

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“…Studies using semi-quantitative scoring of IHC to describe TILs in head and neck squamous cell carcinomas have suggested a potential predictive role of infiltrating CD3 + and CD8 + T cells [244,245]. High levels of CD3 + and CD8 + iTILs correlated with improved outcome following definitive chemoradiotherapy, while sTILs showed no significant association [244].…”

Section: Tils In Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…High levels of CD3 + and CD8 + iTILs correlated with improved outcome following definitive chemoradiotherapy, while sTILs showed no significant association [244]. In a subsequent cohort of 161 patients treated with surgery followed by adjuvant chemoradiation, CD3 + and CD8 + TILs in the stromal, intra-tumoral and tumor periphery compartments were all associated with improved outcome [245]. Large prospective clinical trials of treatment modalities would be an ideal setting to further investigate the potential role of TILs in predicting the efficacy of chemoradiation in head and neck squamous cell carcinomas.…”

Section: Tils In Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

571

366

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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“…(4) This efficacy highlights the immunogenic nature of SCCHN and supports that immune-based therapies are a rational and promising therapeutic platform for SCCHN. CD8 þ T-cell infiltration has been associated with better overall survival and response to chemoradiotherapy in human papilloma virus (HPV)-positive and HPV-negative patients with locoregionally advanced SCCHN, though this still remains controversial and further studies are needed to confirm these findings (5)(6)(7)(8)(9). Previous work has shown that CD8 þ T-cell enhances the efficacy of radiotherapy through activation of CD8 þ T-cell-mediated cytotoxicity and a decrease in tumor infiltration by myeloid-derived suppressor cells (MDSC; refs.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Saloura

Fatima

Zewde

et al. 2017

Clinical Cancer Research

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Purpose: Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with a suboptimal 5-year overall survival of approximately 50% with surgery and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited. Immunotherapy with checkpoint blockade has emerged as a promising option for patients with recurrent/metastatic SCCHN; however, it has not been investigated in the curative-intent setting yet. The purpose of this study was to investigate the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease.Experimental Design: We performed T-cell receptor sequencing of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy and correlated the T-cell clonality and the mRNA expression levels of immune-related genes with clinicopathologic parameters.Results: Clonal expansion of T cells was significantly higher in human papilloma virus (HPV)-negative compared with HPVpositive tumors, signifying more robust antigen presentation in HPV-negative tumors. The latter was supported by the higher percentage of HPV-negative tumors expressing HLA-A protein compared with HPV-positive tumors (P ¼ 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P ¼ 0.003) independent of tumor size, nodal stage, and HPV status.Conclusions: Our findings support clonal expansion of T cells in SCCHN patients with locoregionally advanced disease and imply differences in the antigen presentation capacity between HPV-negative and HPV-positive tumors. Elevated GRZB mRNA levels may also serve as a favorable and independent predictor of outcome in SCCHN patients treated with chemoradiotherapy. These data provide rationale for the introduction of immunotherapeutic approaches in the curative-intent setting.

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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)

Cited by 176 publications

References 48 publications

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

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