Research Article - Biomedical Research (2017) Volume 28, Issue 2
Immunogenic chemotherapy sensitizes non-small cell lung cancer to immune checkpoint blockade therapy in preclinical models
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.Author(s): Jun Lu, Ying Zhu, Jiashun Wang, Lufeng Wang, Yikai Chen, Weipeng Cai, Jinquan Yuan, Xiaokang Wang