资源介绍
Metastatic colorectal cancer (CRC) is a major cause of cancer-related death and incidence is rising in the younger population (<50 years). ?Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. ?The present study investigates the impact of chemotherapy on the tumor immune microenvironment. ?We treat human liver metastases slices with 5-Fluorouracil (5FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. ?Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression of PD-1 ligands in response to 5FU+irinotecan. ?Conversely, immune checkpoint TIM-3 ligands are maintained or up-regulated by chemotherapy in CRC with an enterocyte-like signature, and combining chemotherapy with TIM-3 blockade leads to synergistic tumor killing. ?Together, our analyses highlight chemo-modulation of the immune microenvironment and provide a framework for combined chemo-immunotherapies.?
