Gemcitabine and celecoxib synergistically promote antitumor efficacy of αPD-1 by triggering immunogenic cell death

Author:

Zhu Xiongjie1,Yang Xia1,Yu Zhongjian1,Cai Rui1,Li Ying2,Zhou Min1,Zheng Yanfang1

Affiliation:

1. Affiliated Cancer Hospital & Institute of Guangzhou Medical University

2. Zhujiang Hospital of Southern Medical University

Abstract

Abstract There is emerging evidence that immunogenic chemotherapy is not only cytotoxic toward tumor cells but also ameliorates the immunosuppressive tumor microenvironment by inducing immunogenic cell death (ICD) to achieve long-lasting antitumor efficacy. However, comprehensive analysis of ICD inducers is lacking in lung cancer. We investigated the ability of five chemotherapeutic agents to trigger ICD. And further study of how gemcitabine (GEM) activates antitumor immunity and synergistic enhancement of antitumor immunochemotherapy. Herein, we observed that GEM induced characteristics of ICD. Moreover, we demonstrated that celecoxib could enhance ICD by attenuation of indoleamine 2,3-dioxygenase 1 (IDO-1) expression and augmentation of ROS-based endoplasmic reticulum stress. In the present study, we found the combination of GEM, celecoxib and anti-PD-1 monoclonal antibody (aPD-1) exhibited potent antitumor activity and long-term antitumor efficacy in immunocompetent mice by synergistic anti-tumor activity and recruitment of tumor infiltrating lymphocytes. These results support a combination of GEM, celecoxib and aPD-1 as a potential treatment regimen for patients with lung cancer.

Publisher

Research Square Platform LLC

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