Effect of Chemotherapeutics on In Vitro Immune Checkpoint Expression in Non-Small Cell Lung Cancer

化疗对非小细胞肺癌体外免疫检查点表达的影响

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作者:Yu Zhao, Zhe Wang, Xiuhuan Shi, Ting Liu, Wenwen Yu, Xiubao Ren, Hua Zhao

Conclusion

Chemotherapy agents have different effects on the expression of ICP ligands in tumor cells with different pathological types, and this may affect the efficacy of combined immunotherapy. These results provide a theoretical basis for further selection and optimization of the combination of chemotherapy and immunotherapy.

Methods

Several first-line chemotherapy agents (cisplatin, carboplatin, paclitaxel, gemcitabine, vinorelbine, and pemetrexed) were selected to treat different NSCLC cell lines (squamous carcinoma H1703, adenocarcinoma A549, and large cell cancer H460) for 72 hours, and then the changes in ICP expression in the tumor cells were observed through flow cytometry.

Results

Cisplatin, carboplatin, and paclitaxel upregulated the expressions of programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2) in A549 and H460 cell lines. Meanwhile, vinorelbine and pemetrexed upregulated PD-L1 and PD-L2 in H1703, A549, and H460 cell lines. Paclitaxel, gemcitabine, vinorelbine, and pemetrexed significantly upregulated the expressions of both galectin-9 and high-mobility group box protein 1 (HMGB1) in the A549 cell line. Cisplatin and paclitaxel significantly upregulated the expressions of major histocompatibility complex-II (MHC-II), galectin-3, α-synuclein, and fibrinogen-like protein 1 (FGL1) in A549 and H460 cell lines. In addition, cisplatin and vinorelbine significantly upregulated the expressions of both CD155 and CD112 in the H460 cell line. Vinorelbine upregulated MHC-I in all three cell lines.

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