Overview
- Weill Cornell researchers report in Nature Immunology (Nov. 17, 2025) that tumors co-opt a thrombospondin‑1 interaction to suppress anti‑tumor immunity.
- Tumor‑produced TSP‑1 engages CD47 on T cells to trigger calcineurin–NFAT signaling that elevates TOX and inhibitory receptors, weakening effector activity.
- CD47 is markedly upregulated on exhausted tumor‑infiltrating CD8+ T cells in both human and mouse samples.
- Genetic loss of CD47 or thrombospondin‑1 in mice reduced T‑cell exhaustion and delayed tumor growth, with CD47‑deficient T cells better controlling melanoma.
- A peptide disruptor (TAX2) preserved cytokine production and tumor infiltration in melanoma and colorectal models, showed synergy with PD‑1 blockade, and is being advanced as a potential therapeutic strategy.