Spatial genomics reveals cholesterol metabolism as a key factor in colorectal cancer immunotherapy resistance.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across multiple cancer types achieving durable responses for a significant number of patients. Despite their success, many patients still fail to respond to ICIs or develop resistance soon after treatment. We sought to identify early treatment features associated with ICI outcome. We leveraged the MC38 syngeneic tumor model because it has variable response to ICI therapy driven by tumor intrinsic heterogeneity. ICI response was assessed based on the level of immune cell infiltration into the tumor - a well-established clinical hallmark of ICI response. We generated a spatial atlas of 48,636 transcriptome-wide spots across 16 tumors using spatial transcriptomics; given the tumors were difficult to profile, we devel

SUBMITTER: Kavran AJ 

PROVIDER: S-EPMC11959564 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature