Author：Chengzhi Zhou, Yanhui Chen, Ying Hu, Yang Liu, Henghui Zhang

Background: The previous study indicated that the biomarkers of molecular alterations and tumor immunity in the microenvironment could predict the response of immunotherapy in NSCLC patients. However, the cross talk between the two factors is unclear. This study was designed to investigated the features of tumor immunity in the microenvironment of deferential molecular characterization in NSCLC patients. 

Methods: Tumor tissue and matched blood samples from 62 patients with NSCLC were collected. The mutation profiles were sequenced by a cancer gene-targeted NGS panel. The PD-L1 expression and immune cells infiltrated in tumor microenvironment were detected by multiplex immunofluorescence staining. 

Results: The distinct of molecular alterations showed the different tumor microenvironments in terms of immune cell composition and of PD-L1 expression by tumor cells in NSCLC. KRAS-mutated tumors were characterized by higher level of PD-L1 expression and lower NK cells infiltrated in tumor area than KRAS-wild type tumor. TP53-mutated tumors were characterized by higher CD8+T cell and lower NK cells infiltrated in tumor area. In contrast, EGFR-mutated tumors were characterized by lower level of PD-L1 expression and higher NK cells. Moreover, we found that the PD-L1 expression increased in MET gene CNV gain tumors than MET wild type tumors. 

Conclusions: The features of tumor immunity in the microenvironment changed in deferential molecular characterization in NSCLC. it may help to explain the phenomenon that the efficacy of immunotherapy changed in deferential molecular characterization of NSCLC.