Tumor infiltrating T cells influence prognosis in stage I-III non-small cell lung cancer

T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4⁺ T helper cells (T_h), CD8⁺ cytotoxic (T_c) and FOXP3⁺ regulatory T (T_reg) cells in NSCLC, we performed this analysis.

By counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral T_h cells, T_reg cells and T_c cells in n=294 NSCLC patients with pTNM stage I-III disease.

Strong CD4⁺ infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4⁺ infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio <1 was associated with high grade NSCLC tumors (P=0.020). High CD8⁺ T cell infiltration was an independent prognostic factor for OS (P=0.040) and progression-free survival (PFS) (P=0.012) in the entire study collective. The OS benefit of high CD8⁺ infiltration was especially prominent in PD-L1 negative NSCLC (P=0.001) but not in PD-L1 positive tissue (P=0.335). Moreover, positive FOXP3⁺ expression in tumor infiltrating lymphocytes was associated with increased OS (P=0.007) and PFS (P=0.014) in SCC but not in ADC and LCC (all P>0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236).

High proportion of CD8⁺ T_c cells correlated with improved prognostic outcome in stage I-III NSCLC. T_h cells and T_reg cells have implications on outcome with respect to tumor histology and biology.