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.