Colorectal cancer scRNA-seq 10xG-format data matrix

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.