Tumor-associated microbiota suppresses anti-tumor immunity by driving cDC1 dysfunction in lung adenocarcinoma
Immunosuppressive microenvironment formation during tumor progression leads to either resistance or nondurable response to anti-PD1 immune checkpoint inhibitor therapy. Besides tumor-infiltrating immune cell populations being reshaped, the local microbiota was undergoing dysbiosis along with the development of lung cancer in both mice and human patients. It is unclear whether increased intratumoral bacteria were involved in the remodeling of tumor-infiltrated immune cells, especially interfering with cDC1 and therefore dampening its downstream anti-tumor CD8+ T cell responses. To address this question, we induced lung adenocarcinoma in SPF and GF KrasLoxp-Stop-Loxp-G12D;p53fl/fl (KP) mice by the intratracheal instillation of lentivirus or adenovirus expressing Cre recombinase and performed CITE-seq to profile the total tumor-infiltrated immune cell populations in both SPF and GF tumor-bearing lungs. To further investigate the transcription differences in cDC1 of SPF and GF tumors, we sorted tumor-infiltrated cDC1 and performed bulk RNA sequencing.