Programmed cell death-ligand 1 expression and CD8 positive tumor-infiltrating lymphocyte density in non-small cell lung carcinoma and its association with histopathological grading.

Abstract

Non-small cell lung carcinoma (NSCLC), comprising 85% of lung cancers, remains a leading cause of cancer mortality despite advances in treatment. Immunotherapy, particularly immune checkpoint inhibitors targeting the PD-1/PD-L1 axis, has revolutionized therapy, though outcomes vary. This study aimed to explore the association between PD-L1 expression, CD8 tumor-infiltrating lymphocyte (TIL) density, and histopathological grading in NSCLC. Our retrospective, single-centered cohort comprised 64 biopsy samples of NSCLC. PD-L1 and CD8 TILs density was assessed through immunohistochemistry. We also classified the tumors into four groups based on the PD-L1 and CD8-positive TIL statuses and evaluated their association with clinicopathological parameters. Male subjects were the predominant population in the study group (86%), with a mean age of 60 years. Most of the cases were smokers/ex-smokers (70.3%). Among 64 cases, PD-L1 positivity was observed in 62.5%, correlating with poorly differentiated tumors (grade 3) (p=0.03), suggesting its association with poor prognosis. Among PD-L1 positive cases, 55% had high expression and 45% had low expression. CD8 TIL density was low in 62.5% of cases and showed no significant correlation with clinical variables. Combined analysis revealed that 42.19% of cases were PD-L1+/CD8 low, a phenotype indicative of immune evasion and aggressive tumor behavior. Overall, our results emphasize that while PD-L1 immunohistochemistry remains a critical tool for identifying candidates for immunotherapy, it is not a standalone predictor of treatment response. Integrating CD8 TIL density provides additional prognostic information, potentially guiding more personalized treatment strategies.