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Immunogenic chemotherapy sensitizes non-small cell lung cancer to immune checkpoint blockade therapy in preclinical models

Jun Lu, Ying Zhu, Jiashun Wang, Lufeng Wang, Yikai Chen, Weipeng Cai, Jinquan Yuan, Xiaokang Wang

Background: Lung cancer is the top common cancer and cause of cancer-related death worldwide. Checkpoint blockade immunotherapies have shown extraordinarily anti-tumor effects, but only benefit the minority of patients whose tumors are pre-infiltrated by CD8+ T cells. However, the majority of solid tumors, including lung cancer are not immunogenic and CD8⁺ T cell infiltration is inconspicuous.

Purpose: We aimed to explore the potential favourable roles of chemotherapy in promoting immune checkpoint blockade therapy in non-small cell lung cancer (NSCLC).

Method: We combined chemotherapy gemcitabine with immune checkpoint blockade therapy anti-PD-1 antibody in preclinical models of NSCLC. Survival analysis and potential mechanisms were also analysed.

Result: We found that lung cancer lacks CD8⁺ T cell infiltration and resisted to anti-PD-1 antibody when used alone. When combined with chemotherapy drug gemcitabine, more CD8⁺ T cell infiltration was seen and effects of anti-PD-1 antibody were significantly enhanced. Animals in the combination therapy group showed longer survival time than gemcitabine or anti-PD-1 antibody therapy groups.

Conclusion: In conclusion, our findings suggested that chemotherapy stimulated immunogenic potential of NSCLC and synergized with immune checkpoint blockade therapy.