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

Nat Commun. 2020 Nov 30;11(1):6119. doi: 10.1038/s41467-020-19973-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemokine CCL7 / deficiency
  • Chemokine CCL7 / genetics
  • Chemokine CCL7 / metabolism*
  • Chemokine CCL7 / pharmacology*
  • Chemokines / metabolism
  • Disease Models, Animal
  • Female
  • Genes, ras
  • Humans
  • Immunity*
  • Immunotherapy / methods*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tumor Microenvironment / immunology
  • Tumor Suppressor Protein p53


  • Antibodies, Monoclonal, Humanized
  • CCL7 protein, human
  • Ccl7 protein, mouse
  • Chemokine CCL7
  • Chemokines
  • TP53 protein, human
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • atezolizumab