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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.