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Aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impedes antitumor immunity and instigates immune evasion. The remarkable efficacy of immune checkpoint blockade has been confirmed in various solid tumors. However, the correlation between PD-L1 expression and host immunological landscape remains of considerable controversy in non-small cell lung cancer (NSCLC). In the present study, PD-L1 expression and CD8 + tumor-infiltrating lymphocyte (TIL) infiltration levels were determined by immunohistochemistry (IHC) in tumor sections of 138 NSCLC patients. The expression level of PD-L1 was positively correlated with the abundance of CD8 + TILs ( p < 0.0001). Furthermore, no constitutive expression of PD-L1 was observed in the majority of six NSCLC cell lines detected by Western blot; but exposure to interferon-γ (IFN-γ), a primary cytokine secreted by activated CD8 + T cells, prominently increased PD-L1 expression. Notably, a significantly positive association was determined within PD-L1, CD8 and IFN-γ gene expression by qRT-PCR, which was corroborated by RNA-sequencing from TCGA lung cancer dataset. These findings demonstrate that PD-L1 expression indicates an adaptive immune resistance mechanism adopted by tumor cells in the aversion of immunogenic destruction by CD8 + TILs. Both higher expression of PD-L1 and infiltration of CD8 + TILs were correlated with superior prognosis ( p = 0.044 for PD-L1; p = 0.002 for CD8). Moreover, Cox multivariate regression analysis showed that the combination of PD-L1 and CD8 were independent prognostic factors, which was more accurate in prediction of prognosis in NSCLC than individually. Finally, we found that IFN-γ induced the upregulation of PD-L1 in NSCLC cells, mainly through the JAK/STAT1 signaling pathway. In conclusion, PD-L1 expression is mainly induced by activated CD8 + TILs via IFN-γ in the immune milieu and indicates pre-existing adaptive immune response in NSCLC.

Granulocyte colony-stimulating factor (G-CSF) is a kind of hematopoietic growth factor which is produced by monocytes, fibroblasts and endothelial cells. G-CSF acts on neutrophilic progenitor cells by binding to specific cell surface receptors, thereby stimulates proliferation, differentiation, commitment, and selected end-cell functional activation including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing and the increased expression of some functions associated with cell surface antigens. G-CSF is effective and safe for treatment of neutropenia. In this paper, structure of G-CSF and its mechanism, recent status of research on G-CSF, pharmacokinetics, clinical application, adverse effects and prospect of G-CSF are mainly reviewed.