NextGen Omics Data & Analysis

Colorectal cancer frequently progresses to liver metastases (CRLM), a stage with limited treatment options and poor prognosis. Surgical resection is the only curative treatment, but many patients require neoadjuvant therapy to downstage their tumors and become eligible for surgery. However, a significant proportion fail to respond, and the mechanisms underlying this variability in treatment response remain largely unknown. To uncover markers associated with treatment response, we profiled T cell states and their spatial organization in CRLM. We discovered that the organization and functional polarization of CD4 memory T cell networks define treatment outcome. In responders, Th1-polarized CD4 memory T cells assembled with progenitor-like CD8 T cells and specialized antigen-presenting cells (APCs) into organized, pro-immunogenic niches that supported coordinated effector activity. In contrast, non-responders lacked these organized networks, displaying myeloid-rich regions dominated by circulating-like CD4 memory and regulatory T cells. These findings identify CD4 memory-driven immune niches as key determinants of chemotherapy efficacy, establishing a framework for biomarker discovery and rational immunotherapy strategies in metastatic colorectal cancer.