Colorectal cancer scRNA-seq 10xG-format data matrix

<p>Metastatic colorectal cancer (CRC) is a major cause of cancer-related death and incidence is rising in the younger population (&lt;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. </p>