IMMUNOLOGY2024™ Conference Recordings-Spatially organized immune hubs in colon cancer

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Video Summary

Karin Perka presented work on “immune hubs” in colon cancer: spatially organized groups of immune, cancer, and stromal cells that function together rather than as isolated cell types. She contrasted mismatch repair-deficient colorectal tumors, which are highly mutated, immune-infiltrated, and often responsive to anti-PD-1 therapy, with mismatch repair-proficient tumors, which make up most colon cancers and are usually immunotherapy-resistant.<br /><br />Using single-cell RNA sequencing on about 400,000 cells from tumor and normal tissue, the team identified 204 gene programs and used them to define coordinated cell networks. One key pattern was an “anti-tumor immunity hub” found mainly in mismatch repair-deficient tumors, involving CXCL13-positive T cells, interferon-stimulated myeloid and cancer cells, and chemokine feedback loops that recruit more T cells. They validated these structures in tissue by spatial staining, showing they form at tumor-stroma interfaces.<br /><br />They then studied a clinical trial combining BRAF/MEK inhibition with anti-PD-1 in mismatch repair-proficient metastatic colon cancer. In responding patients, some hub-associated programs were induced on treatment, suggesting therapy can partially rewire the tumor microenvironment.<br /><br />Finally, they used spatial transcriptomics (Merscope/MERFISH-like profiling) to map these hubs in greater detail, revealing distinct immune, inflammatory, and lymphoid regions and setting up future work to find new therapeutic targets.

Keywords

colon cancer

immune hubs

mismatch repair-deficient

mismatch repair-proficient

single-cell RNA sequencing

anti-PD-1 therapy

spatial transcriptomics