Memory CD4 T cells orchestrate neoadjuvant-responsive niches in colorectal cancer liver metastases
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Colorectal cancer frequently progresses to liver metastases (CRLM), a stage with poor prognosis. Surgical resection offers the best chance of cure, but most patients are initially ineligible. Neoadjuvant therapy can enable resection, yet response rates remain low, and mechanisms are unclear. To uncover markers associated with treatment efficacy, we profiled T cell states and their spatial organization in CRLM. We reveal distinct immune architectures, with the tumor center enriched in exhausted, regulatory, and memory T cells, but depleted of cytotoxic subsets. Responders feature CD4-coordinated niches with activated Th1-like CD4 memory T cells, stem-like and effector CD8 T cells, and spatially organized antigen-presenting cells. In contrast, non-responders harbor disorganized, myeloid-rich niches with less activated CD4 memory T cells and abundant regulatory T cells. These findings highlight activated CD4 memory T cells and their spatial niches as key markers of neoadjuvant response, offering a framework for biomarker discovery and rational immunotherapy design.
