The tumor immune microenvironment and its implications for clinical outcome in patients with oropharyngeal squamous cell carcinoma

Abstract

Background: We examined PD-L1 expression on tumor cells (TCs) and immune cells (ICs) and density of CD3⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigated their significance on clinicopathological characteristics and clinical outcomes.

Methods: In a cohort of 65 patients treated by definitive intensity-modulated radiotherapy (IMRT) with curative intent, immunohistochemical analysis of PD-L1 expression on TCs and ICs, and TIL subtyping was performed on primary biopsy tumor tissues, followed by prognostic evaluation of these immune response-related parameters including classification into four tumor immune microenvironment (TIM) types. To evaluate HPV status, p16 immunohistochemistry was performed.

Results: Densities of CD3⁺ and CD8⁺ TILs and PD-L1 expressions on TCs and ICs were significantly higher in p16+/HPV-mediated OPSCC. Patients with high densities of stromal CD8⁺ TILs displayed significantly better overall survival (OS) and progression-free survival (PFS). PD-L1 expression neither on tumor cells nor on immune cells affected survival outcomes. Distribution of TIM types based on the combination of PD-L1 expression on TCs and densities of CD8⁺ TILs is significantly different in p16+ compared with p16- OPSCC. In type III TIM (TC-PD-L1+/low CD8⁺ TIL density), significantly better OS was shown in p16+ group compared with p16- OPSCC.

Conclusion: The prognostic and predictive role of tumor immune microenvironment was confirmed for patients with OPSCC. Combining HPV status with the evaluation of densities of CD8⁺ TILs and PD-L1 expression including TIM classification might be of high clinical interest and warrants further prospective evaluation.

Keywords: CD8; HPV; PD-L1; oropharyngeal squamous cell carcinoma; tumor-infiltrating lymphocytes.