1. CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer
- Author
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Yu-Ting Dong, Rui Huang, Dandan Lin, Xindong Liu, Fang-Fang Liu, Man Zhang, Peng Zhang, Bo Zhong, Qian Chu, Yaqi Duan, Peng Wang, Yu Deng, and Wei Yang
- Subjects
CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Lung Neoplasms ,medicine.medical_treatment ,General Physics and Astronomy ,CD8-Positive T-Lymphocytes ,Mice ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Tumor Microenvironment ,Chemokine CCL7 ,Mice, Knockout ,Multidisciplinary ,respiratory system ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Tumour immunology ,Female ,Immunotherapy ,Chemokines ,Adjuvant ,endocrine system ,T cell ,Science ,Antibodies, Monoclonal, Humanized ,CCL7 ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,medicine ,Animals ,Humans ,Lung cancer ,Tumor microenvironment ,business.industry ,Immunity ,General Chemistry ,medicine.disease ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,Genes, ras ,030104 developmental biology ,Cancer research ,sense organs ,Tumor Suppressor Protein p53 ,business ,CD8 - Abstract
The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL−G12D/+Tp53fl/fl (KP) and the KrasLSL−G12D/+Lkb1fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+ and CD4+ T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC., Only a limited proportion of patients with non-small cell lung cancer respond to anti-PD-1/PD-L1 immunotherapy. Here, the authors show that in autochthonous models of KRAS-mutated lung cancer, CCL7 promotes cDC1 infiltration into the lungs, sustaining antitumor immune responses and potentiating anti-PD1 treatment efficacy.
- Published
- 2020