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Abstract
Introduction: The research demonstrates that head and neck squamous cell carcinoma (HNSCC) frequently exhibits an immunosuppressive microenvironment, despite immune cell infiltration into the tumor. This phenomenon significantly affects treatment outcomes and underscores the need to identify new prognostic markers and therapeutic targets.
Aim: To investigate the subpopulations of tumor-infiltrating lymphocytes in oropharyngeal squamous cell carcinoma (OPSCC) and the type of PD-L1 expression (CPS, TPS) with regard to both HPV status and gender.
Materials and Methods: From 2020 to June 2022, a research study was conducted by the Department of Oncology at Kuban State Medical University, located at Clinical Oncology Dispensary No. 1 in Krasnodar city. The study included 65 p16-negative (52 %) and 60 p16-positive (48 %) patients with OPSCC. The levels of tumor-infiltrating lymphocytes (TILs) were assessed in 86 patients. Immunohistochemical (IHC) analysis was conducted to examine the components of the tumor immune microenvironment for CD4, CD8, CD68, CD163, CD20 IHC markers, as well as PD-L1 and Ki-67 expression. Statistical analysis was performed using IBM SPSS Statistics V22 software.
Results: The research found that HPV-positive status was associated with palatine tonsil cancer (p = 0.021) and high levels of tumor-infiltrating lymphocytes (TILs) (p = 0.007), possibly due to Tregs, as there was a more significant association with CD4+ TILs (p = 0.007) than with CD8+ TILs (p = 0.033). In women, OPSCC was more often represented by tonsil cancer (p < 0.001), which was characterized by high values of CD4+ TILs (p = 0.021) and CD8+ TILs (p = 0.035), but a higher CD4/CD8 immunoregulatory index (IRI) (p = 0.021). TILs ≥ 50 % were associated with high levels of CD4+TILs and CD8+TILs (p < 0.001 and p = 0.005, respectively). Women also demonstrated a high level of PD-L1 expression on tumor cells using both the tumor proportion score (TPS) (p = 0.009) and the combined positive score (CPS) (p = 0.018). Tumors with CD4+TILs < 30 % revealed high values of CPS and TPS (p = 0.001, p = 0.005, respectively), as well as CD68 < 8.5 % (p = 0.001). N+ was associated with a high level of PD-L1 CPS. Patients under 55 revealed a higher level of the CD20+B-lymphocyte marker (p = 0.02). Expression of p53 ≥ 50 was associated with a lower level of CD20 expression (p < 0.001). The level of CD4+TILs ≥ 30 was associated with higher CD20 rates (p = 0.002).
Conclusion: The components of the tumor microenvironment in OPSCC and the degree of immunosuppression are dependent on the patient's p16 (HPV) status, gender, and age.
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