PD-L1 Lymphocytes Are Associated with CD4, Foxp3CD4, IL17CD4 T Cells and Subtypes of Macrophages in Resected Early-Stage Non-Small Cell Lung Cancer.

The non-canonical PD-L1 pathway revealed that programmed-death ligand 1 (PD-L1) expression in immune cells also plays a crucial role in immune response. Moreover, immune cell distribution in a tumour microenvironment (TME) is pivotal for tumour genesis. However, the results remain controversial and further research is needed. Distribution of PD-L1-positive (PD-L1) tumour-infiltrating lymphocytes in the context of TME was assessed in 72 archival I-III stage surgically resected NSCLC tumour specimens. Predominant PD-L1 lymphocyte distribution in the tumour stroma, compared to islets, was found ( = 0.01). Higher PD-L1 lymphocyte infiltration was detected in smokers due to their predominance in the stroma. High PD-L1 lymphocyte infiltration in tumour stroma was more common in tumours with higher CD4 T cell infiltration in islets and stroma, Foxp3CD4 T cell infiltration in islets and lover M1 macrophage infiltration in the stroma ( = 0.034, = 0.034, = 0.005 and = 0.034 respectively). Meanwhile, high PD-L1 lymphocyte infiltration in islets was predominantly found in tumours with high levels of IL-17ACD4 T cells in islets and Foxp3CD4 T cells in islets and stroma ( = 0.032, = 0.009 and = 0.034, respectively). Significant correlations between PD-L1 lymphocytes and tumour-infiltrating CD4, Foxp3CD4, IL-17ACD4 T cells and M2 macrophages were found. An analysis of the tumour-immune phenotype revealed a significant association between PD-L1 expression and IL17CD4 and Foxp3CD4 immune phenotypes. PD-L1 lymphocytes are associated with the distribution of CD4, Foxp3CD4, IL17ACD4 T cells, M1 and M2 macrophages in TME of resected NSCLC.