Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells

Shuai Zhang; Yumei Li; Shuqing Liu; Pei Ma; Mengfei Guo; E. Zhou; Limin Duan; Jinshuo Fan; Tingting Liao; Qi Tan; Xuan Wang; Feng Wu; Yang Jin

doi:10.1038/s41419-022-05176-y

Cell Death and Disease (Sep 2022)

Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells

Shuai Zhang,
Yumei Li,
Shuqing Liu,
Pei Ma,
Mengfei Guo,
E. Zhou,
Limin Duan,
Jinshuo Fan,
Tingting Liao,
Qi Tan,
Xuan Wang,
Feng Wu,
Yang Jin

Affiliations

Shuai Zhang: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yumei Li: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Shuqing Liu: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Pei Ma: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Mengfei Guo: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
E. Zhou: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Limin Duan: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jinshuo Fan: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Tingting Liao: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Qi Tan: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xuan Wang: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Feng Wu: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yang Jin: Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Diseases of National Health Commission, Clinical Research Center for major respiratory diseases in Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

DOI: https://doi.org/10.1038/s41419-022-05176-y
Journal volume & issue: Vol. 13, no. 9
pp. 1 – 12

Abstract

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Abstract A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

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