Abstract
Carcinogenesis of human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative (–) OPSCC. HPV-related immune-escape-mechanism could be responsible for the development and progression of HPV+ tumors and an immunophenotype different from HPV– OPSCC is expected. The purpose of this study was to analyze the expression of programmed cell death protein 1 ligand 1 (PD-L1) and its prognostic relevance in relation to CD8+ tumor infiltrating lymphocytes (TILs) and the major histocompatibility complex (MHC) I expression in OPSCC. We quantified PD-L1 expression on tumor cells (TC) and macrophages and MHC I expression in association to CD8+ TILs by immunohistochemistry on tissue microarray derived from 171 HPV+/-OPSCC. HPV-status was determined by p16INK4a immunohistochemistry/HPV-DNA detection. Presence of CD8+ TILs, PD-L1 expression on TC, and a more frequent loss of MHC I in HPV+ compared to HPV- OPSCC was detected. A high amount of CD8+ TILs in the whole cohort and in HPV+ OPSCC and PD-L1 expression on TC in HPV- OPSCC was associated with favorable overall survival. There was a trend for an improved outcome according to PD-L1 expression (macrophages) in HPV+ OPSCC without reaching statistical significance. CD8+ TILs and PD-L1-expression have prognostic impact in OPSCC and might present useful biomarkers for predicting clinical outcome and personalized therapy concepts.
Highlights
Human papillomavirus (HPV) is accepted as a pivotal risk factor for development of oropharyngeal squamous cell carcinoma (OPSCC) and rising incidences have been reported from several countries [1,2,3]
In this study we demonstrate upregulation of programmed cell death 1 ligand 1 (PD-L1) on tumor cells (TC), a high infiltrate of CD8+ tumor infiltrating lymphocytes (TILs) and downregulation of major histocompatibility complex (MHC) I in human papillomavirus (HPV)-related OPSCC
In HPV-related OPSCC a high number of CD8+ TILs was associated with favorable overall survival (OS) in multivariate analysis, whereas in HPV-negative OPSCC high PD-L1 expression on TC was an independent predictor for an improved outcome
Summary
Human papillomavirus (HPV) is accepted as a pivotal risk factor for development of oropharyngeal squamous cell carcinoma (OPSCC) and rising incidences have been reported from several countries [1,2,3]. With a prevalence of more than 80%, high risk HPV16 is the most common type detected in OPSCC [4,5]. OPSCC are known to present levels of heterogeneity and immune escape mechanism highly depend on the tumor and its characteristics itself [7,8]. Evasion strategies are often employed to escape the host immune system. HPV-related OPSCC are preferentially located in lymphoid tissue (tonsil, base of tongue) and dysregulation of the immune system in their surrounding might play an important role in carcinogenesis
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