Single-cell immune profiling of blood and thrombus in cancer-associated thrombosis

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer, but the immune landscape of the thrombus itself is poorly mapped. We combined high-parameter mass cytometry of paired peripheral blood and venous thrombi from non-cancer deep vein thrombosis (DVT) and CAT with an integrated single-cell RNA-sequencing atlas to profile immune remodeling at single-cell resolution. Relative to non-cancer DVT, CAT thrombi showed expansion of CXCR3 + CD11b + myeloid subsets, loss of conventional CD4 + and CD8 + T cells, and accumulation of unconventional double-negative T cells, alongside systemic depletion of T-bet + EOMES + natural killer (NK) cells. We also detected PD-L1 on the CD45 − non-immune compartment of CAT thrombi and found a positive association between hemoglobin and FOXP3 + CD8 + T cells. These exploratory findings nominate chemokine- and checkpoint-related pathways for future study and provide an open single-cell resource for thrombo-immunology research.