On November 30, Nature Communications (IF: 12.131) published online the latest research findings by Professor Zhong Bo’s research group from the Medical Research Institute/College of Life Sciences, and the Frontier Science Center for Immunology and Metabolism, Wuhan University. The article describes the important function and mechanism of chemokines CCL7 recruiting cDC1 to promote antitumor immunity and provide new checkpoint immunotherapy for treating non-small cell lung cancer. The paper is entitled CCL7 Recruits cDC1 to Promote Antitumor Immunity and Facilitate Checkpoint Immunotherapy to Non-small Cell Lung Cancer. The co-first authors are PhD student Zhang Man (enrolled in 2016, College of Life Sciences) and PhD student Yang Wei (enrolled in 2019, Medical Research Institute).

Lung cancer is the most prevalent cancer and the leading cause of cancer-related death. Although checkpoint immunotherapy represented by PD-1/PD-L1 antibody greatly improves the survival rate of lung cancer patients, it is only effective in about 20% of patients. Chemokines are cytokines secreted by various cells, having a chemotactic effect on different cells. They are widely involved in regulating cell development, angiogenesis and cell apoptosis, and play a significant role in tumorigenesis, development, metastasis and other physiological and pathological processes. Previous studies on chemokine CCL7 mainly focused on the regulation of infection and inflammation. There are few studies on CCL7 regulating the occurrence and development of tumors. The specific mechanism remains unknown.

Zhong Bo’s team found that in human non-small cell lung cancer tissues, the expression level of chemokine CCL7 was perceptibly higher than that of normal tissues, which showed a significantly positive correlation with the infiltration of DC cells in tumor tissues and overall patient survival. In the KrasLSL-G12D/+Tp53fl/fl mouse non-small cell lung cancer model, knocking out CCL7 promoted lung cancer progression in mice and shortened their survival time. Further research indicated that CCL7 promoted the infiltration of cDC1 cells in the tumor microenvironment, induced the expansion of T cells in lung cancer tissues and bronchial lymph nodes, and therefore stimulated antitumor immune responses. Previous studies had shown that the efficacy of checkpoint immunotherapy to non-small cell lung cancer depended on the lymphocytes infiltrated by the tumor. Based on that CCL7 promoted the infiltration of cDC1 in tumors and then accelerated the expansion of T cells in tumor tissues, Zhong Bo’s group further found that intranasal injection of CCL7 can prominently enhance the efficacy of PD-1 antibody in KrasLSL-G12D/+Tp53fl and KrasLSL-G12D/+Lkb1fl/fl non-small cell lung cancer mouse models. The study provides new ideas and potential drug targets for improving the efficacy of immunotherapy by modifying the tumor immune microenvironment in the future.

The research was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, the Natural Science Foundation of Hubei Province, and the Medical Takeoff Program and independent scientific research projects of Wuhan University.

Source: https://news.whu.edu.cn/info/1015/62733.htm

Rewritten by: Dong Xiaoqian

Edited by: Zou Xiaohan and Hu Sijia