CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

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 Kras LSL−G12D/+ Tp53 fl/fl (KP) and the Kras LSL−G12D/+ Lkb1 fl/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.