Background: The characteristics of tumor immune microenvironment are important factors affecting the efficacy of immunotherapy, and there are differences in the distribution of tumor-infiltrating lymphocyte (TIL) subsets in different types of tumors. This study aims to compare the distributions of cluster of differentiation (CD) 4+ and CD4+ T cell subsets of TILs and their clinical significance between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
Methods: The tumor tissues of 78 LUAD and 56 LUSC patients who underwent surgery at The Second Affiliated Hospital of Zhengzhou University between October 2020 and October 2022 were collected, TIL level were detected by pathological observation, and the proportions of CD4+, CD4+ T cell subsets and CD4+/CD4+ ratio in TILs were detected by flow cytometry. These indicators were compared between LUAD and LUSC, and their correlations with clinicopathological characteristics and patient survival were analyzed.
Results: There was no significant difference in the TILs level between LUAD and LUSC (P>0.05). The CD4+/CD4+ ratio in LUSC was lower, and proportion of CD4+ T cells was higher than those in LUAD (all P<0.05). In LUAD, the proportions of CD4+, CD4+ T cells and CD4+/CD4+ were correlated with tumor size or tumor-node-metastasis (TNM) stage, while in LUSC, only the proportions of CD4+ and CD4+ T cells were correlated with tumor size, degree of differentiation or TNM stage. In LUAD patients, higher proportions of CD4+, CD4+ T cells and lower CD4+/CD4+ predicted longer survival, and high CD4+/CD4+ (>1.04) was an independent risk factor for PFS and OS (P<0.05); In LUSC patients, there was no correlation between the proportions of CD4+ T cells, CD4+ T cells and CD4+/CD4+ ratio, and patient prognosis (P>0.05).
Conclusions: There were differences in the distribution and balance of CD4+ and CD4+ TIL subsets between LUAD and LUSC, among which CD4/CD4+ ratio closely affected the prognosis of LUAD patients but had relatively weak prognostic value in LUSC patients due to the restriction of CD4+ T cells.
Keywords: CD4; CD8; Lung adenocarcinoma (LUAD); lung squamous cell carcinoma (LUSC); tumor-infiltrating lymphocytes (TILs).