Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma

Matlung, Sanne Evelien; Kempen, Pauline M.W. van; Bovenschen, Niels; Baarle, Debbie van; Willems, Stefan M.

doi:10.4155/fso.15.88

Cited by 40 publications

(41 citation statements)

References 19 publications

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“…In OPSCC tumors, HPV status is one of the key prognostic variable for survival; however, new and stronger predictors of survival might be identified exploring the interaction between immune cells and tumor cells in the tumor microenvironment. Previous studies investigated the role of the microenvironment in head and neck tumors with contradictory results . Here, we obtained a comprehensive “immune signature” of HPV‐negative and HPV‐positive OPSCCs and we found new potential prognostic markers for survival of OPSCC patients.…”

Section: Discussionmentioning

confidence: 94%

“…Previous studies investigated the role of the microenvironment in head and neck tumors with contradictory results. 10 Here, we obtained a comprehensive "immune signature" of HPV-negative and HPVpositive OPSCCs and we found new potential prognostic markers for survival of OPSCC patients. More specifically, expression of HLA-DP/DQ/DR on tumor cells, the numbers of CD68+ CD163+ TAMs in the tumor-associated stroma, and the numbers of CD8+ FoxP+ cells in the tumor were established in our multivariate analyses as independent prognostic markers of survival in oropharyngeal cancer.…”

Section: Discussionmentioning

confidence: 98%

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HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

et al. 2018

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Background Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is a highly immunogenic tumor and differences in tumor microenvironment might contribute to the improved survival of HPV‐positive OPSCC patient. Methods A comprehensive multivariate analysis with clinical and immune variables (human leukocyte antigen [HLA] I/II, programmed death ligand 1 (PD‐L1), programmed death receptor 1 (PD1), T cells, and macrophages) was performed in 142 OPSCC patients. Results We found an inverse correlation between the expression of HLA class II molecules on tumor cells and CD68+ CD163+ tumor‐associated macrophages (TAMs). High HLA‐DP/DQ/DR expression and low number of TAMs were associated with longer disease‐specific survival and disease‐free survival (DFS). Furthermore, a new population of CD8+ FoxP3+ T cells was correlated with shorter DFS in multivariate analysis. Conclusions \We identified new prognostic markers for patients with oropharyngeal cancer, which can be used for selecting patients that can benefit from immunotherapy.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

et al. 2018

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“…Many studies have reported a higher number of TILs, in particular CD8 + T cells within tumor and stroma, in HPV + tumors compared with HPV − tumors [229–233]. Increased numbers of FOXP3 + T regs , PD-1 + T cells and CD20 + B cells within immune infiltrates in HPV + tumors have also been described [234,235].…”

Section: Tils In Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…Interestingly, a B cell signature distinguished HPV + from HPV − tumors, suggesting B cells rather than T cells account for the increased TILs seen in HPV + tumors [236]. Immunohistochemical studies have shown CD8 + and FOXP3 + TILs to significantly correlate with improved prognosis in oropharyngeal HPV + tumors [229–236] and probably also HPV − tumors [233,236]. …”

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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“…According to several studies, a more prominent immune response is observed in HPV-positive tumors compared to HPV-negative tumors, and some studies suggested that TILs play a more important role in HPVpositive tumors than in HPV-negative tumors [15,48,57,58], which might explain the lack of prognostic value of T-cell markers in our patient cohort. However, there are also studies that suggest the opposite [14,59].…”

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confidence: 99%

Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors

Ruiter

Roest

Brakenhoff

et al. 2020

Cancer Immunol Immunother

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Aim This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology. Methods Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm 2 tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan-Meier curves. Results The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p = < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05). Conclusion This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy. Keywords Head and neck squamous cell carcinoma (HNSCC) · Tumor-infiltrating lymphocytes (TILs) · T cells · Prognostic biomarkers AbbreviationsACE-27 Adult Comorbidity Evaluation-27 AUC Area under the curve CI Confidence interval DFS Disease-free survival FFPE Formalin fixed, paraffin embedded HR Hazard ratio ICC Intraclass correlation coefficient LRC Locoregional control ROC Receiver operating characteristics TMA Tissue microarray

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Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma

Cited by 40 publications

References 19 publications

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors

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