| First Author | Ritzmann F | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 10353 |
| PubMed ID | 31316109 | Mgi Jnum | J:283925 |
| Mgi Id | MGI:6387929 | Doi | 10.1038/s41598-019-46759-8 |
| Citation | Ritzmann F, et al. (2019) IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer. Sci Rep 9(1):10353 |
| abstractText | Chronic obstructive pulmonary disease (COPD) is associated with neutrophilic lung inflammation and CD8 T cell exhaustion and is an important risk factor for the development of non-small cell lung cancer (NSCLC). The clinical response to programmed cell death-1 (PD-1) blockade in NSCLC patients is variable and likely affected by a coexisting COPD. The pro-inflammatory cytokine interleukin-17C (IL-17C) promotes lung inflammation and is present in human lung tumors. Here, we used a Kras-driven lung cancer model to examine the function of IL-17C in inflammation-promoted tumor growth. Genetic ablation of Il-17c resulted in a decreased recruitment of inflammatory cells into the tumor microenvironment, a decreased expression of tumor-promoting cytokines (e.g. interleukin-6 (IL-6)), and a reduced tumor proliferation in the presence of Haemophilus influenzae- (NTHi) induced COPD-like lung inflammation. Chronic COPD-like inflammation was associated with the expression of PD-1 in CD8 lymphocytes and the membrane expression of the programmed death ligand (PD-L1) independent of IL-17C. Tumor growth was decreased in Il-17c deficient mice but not in wildtype mice after anti-PD-1 treatment. Our results suggest that strategies targeting innate immune mechanisms, such as blocking of IL-17C, may improve the response to anti-PD-1 treatment in lung cancer patients. |
