Single-cell immune profiling of blood and thrombus in cancer-associated thrombosis
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Summary 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 CXCR3CD11bmyeloid subsets, loss of conventional CD4and CD8T cells, and accumulation of unconventional double-negative T cells, alongside systemic depletion of T-betEOMESnatural killer (NK) cells. We also detected PD-L1 on the CD45non-immune compartment of CAT thrombi and found a positive association between hemoglobin and FOXP3CD8T cells. These exploratory findings nominate chemokine- and checkpoint-related pathways for future study and provide an open single-cell resource for thrombo-immunology research. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.webp undfig1 anchor portrait graphical abs0015 Highlights • CAT thrombi show myeloid expansion and loss of conventional T cells versus DVT u0010 • Suppressive PD-1PD-L1and CXCR3myeloid subsets accumulate in cancer thrombi u0015 • PD-L1 marks the CD45non-immune compartment of cancer-associated thrombi u0020 • Hemoglobin tracks with FOXP3CD8T cells across blood and thrombus u0025 simple ulist0010 author-highlights abs0020 Immun
Abstract
Summary 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 CXCR3CD11bmyeloid subsets, loss of conventional CD4and CD8T cells, and accumulation of unconventional double-negative T cells, alongside systemic depletion of T-betEOMESnatural killer (NK) cells. We also detected PD-L1 on the CD45non-immune compartment of CAT thrombi and found a positive association between hemoglobin and FOXP3CD8T cells. These exploratory findings nominate chemokine- and checkpoint-related pathways for future study and provide an open single-cell resource for thrombo-immunology research. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.webp undfig1 anchor portrait graphical abs0015 Highlights • CAT thrombi show myeloid expansion and loss of conventional T cells versus DVT u0010 • Suppressive PD-1PD-L1and CXCR3myeloid subsets accumulate in cancer thrombi u0015 • PD-L1 marks the CD45non-immune compartment of cancer-associated thrombi u0020 • Hemoglobin tracks with FOXP3CD8T cells across blood and thrombus u0025 simple ulist0010 author-highlights abs0020 Immunology; Hematology; Cancer teaser abs0025