Comprehensive spatial and immune profiling of metastatic mismatch repair-deficient colorectal cancer reveals response to immunotherapy.

ABSTRACT:

Introduction

Mismatch repair-deficient (dMMR) colorectal cancers (CRCs) exhibit variable clinical responses to immune checkpoint inhibitors (ICIs) despite their high immunogenicity.

Methods

To investigate the molecular and spatial determinants of this heterogeneity, we analyzed five metastatic sites (colon, liver, peritoneum, left ovary, and right ovary) from a dMMR CRC patient treated with pembrolizumab using bulk and single-cell RNA sequencing combined with multiplex immunohistochemistry.

Results

Responsive lesions were characterized by enriched cytotoxic and interferon-γ signatures, greater CD8⁺ T-cell infiltration, and close spatial proximity between programmed death-ligand 1(PD-L1)⁺ tumor cells and M1-like macrophages. In contrast, resistant

SUBMITTER: Park I 

PROVIDER: S-EPMC12898929 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature