Distribution characteristics of infiltrating PD-L1+ lymphocytes in the tumor microenvironment of early-stage NSCLC

<bold>Background:</bold> Programmed death-ligand 1 (PD-L1) is the only, but not the perfect biomarker for immunotherapy selection. There was established, that not only immune cells existence in tumor microenvironment, but also the distribution in tumor tissue are playing important role in immune response and can be a prognostic factor in NSCLC. <bold>Methods:</bold> 72 archival surgically resected stage I-III NSCLC specimens were assessed for PD-L1 expression on tumor infiltrating lymphocytes in ten high power fields. Specimens were already assessed for tumor infiltrating immune cells. <bold>Results:</bold> Predominant infiltration of PD-L1⁺ lymphocytes was observed in tumor stroma compared with islets (median 36.5 vs. 5, <italic>p</italic>= 0.01). Significantly higher PD-L1⁺ lymphocytes infiltration in tumor stroma was seen in smokers, compared with non-smokers (<italic>p</italic>=0.043) and in pT2a-T2b stage, compared with pT1a-T1b (<italic>p</italic>=0.042). Tumors with higher PD-L1⁺ lymphocytes infiltration in stroma had higher infiltration of CD4⁺ T cells in stroma and islets (<italic>p</italic>=0.034, <italic>p</italic>=0.034), Foxp3⁺CD4⁺ T cells in islets (<italic>p</italic>=0.005) and lower M1 macrophages infiltration in stroma (<italic>p</italic>=0.034), compared with lower PD-L1⁺ lymphocytes infiltration. Meanwhile tumors with higher PD-L1⁺ lymphocytes infiltration in islets had higher infiltration of Foxp3⁺CD4⁺ T cells in stroma and islets (<italic>p</italic>=0.034, <italic>p</italic>=0.035) and IL-17A⁺CD4⁺ T cells in islets (<italic>p</italic>=0.032), compared with lower PD-L1⁺ lymphocytes infiltration. There was no association between PD-L1⁺ lymphocytes distribution and survival. <bold>Conclusion:</bold> PD-L1⁺ lymphocytes distribution in early-stage NSCLC were associated with smoking status, tumor size, CD4⁺T cells, Foxp3⁺CD4⁺ T cells, IL-17A⁺CD4⁺ T cells and M1 macrophages.