{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:01:11Z","timestamp":1790798471927,"version":"4.1.0"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The use of anti\u2013programmed cell death-1 (PD-1) antibody increases heart failure (HF) risk in patients with cancer with preexisting cardiovascular conditions. However, the underlying mechanism remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      To evaluate the effects of anti\u2013PD-1 antibody on transverse aortic constriction (TAC)\u2013induced cardiac remodeling and HF, anti\u2013PD-1 antibody\u2013treated mice; T cell\u2013, myeloid-, and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell\u2013specific\n                      <jats:italic toggle=\"yes\">Pdcd1<\/jats:italic>\n                      knockout; C-X-C motif chemokine receptor 3 (\n                      <jats:italic toggle=\"yes\">Cxcr3<\/jats:italic>\n                      ) knockout; and granzyme B (\n                      <jats:italic toggle=\"yes\">Gzmb<\/jats:italic>\n                      ) knockout mice combined with flow cytometry, Western blotting, immunofluorescence staining, pharmacological approaches, and bulk RNA-sequencing analyses were used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Administration of anti\u2013PD-1 antibody, T cell\u2013, or CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell\u2013specific\n                      <jats:italic toggle=\"yes\">Pdcd1<\/jats:italic>\n                      deletion, but not myeloid-specific\n                      <jats:italic toggle=\"yes\">Pdcd1<\/jats:italic>\n                      knockout, aggravated TAC-induced cardiomyopathy and HF in mice. Mechanistically, PD-1 blockade or deletion increased myocardial infiltration of CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, leading to granzyme B\/perforin\u2013mediated impairment of cardiomyocyte mitochondrial complex I to exacerbate TAC-induced cardiac injury and HF. TAC-enhanced chemotaxis, between cardiac fibroblast\u2013derived CXCL9\/CXCL10 and CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, was a driving force for recruiting CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells under the conditions of PD-1 blockade or deletion. The worsened TAC-induced cardiomyopathy caused by anti\u2013PD-1 antibody or T cell\u2013specific\n                      <jats:italic toggle=\"yes\">Pdcd1<\/jats:italic>\n                      deletion was rescued by genetic deletion or pharmacological blockade of granzyme B and CXCR3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Anti\u2013PD-1 antibody enhances myocardial infiltration of CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells under TAC condition through CXCL9\/CXCL10\u2013mediated chemotaxis. The increased granzyme B and perforin likely derived from CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells impair function of mitochondrial respiratory chain complexes to cause cardiomyocyte apoptosis, thereby exacerbating TAC-induced cardiomyopathy and HF. CXCL9\/CXCL10-CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell axis may represent a promising target for combating anti\u2013PD-1 antibody\u2013associated cardiotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.074024","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:01:59Z","timestamp":1788253319000},"page":"1238-1257","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Programmed Cell Death-1 in Cytotoxic CD8\n                    <sup>+<\/sup>\n                    T Cells Exacerbates Pressure Overload\u2013Induced Cardiac Injury"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6861-6376","authenticated-orcid":true,"given":"Ming-Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."},{"name":"Departments of Cardio-Oncology and Pharmacy and Oncological Surgery, Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Heilongjiang Key Laboratory for Metabolic Disorder and Cancer Related Cardiovascular Diseases, China (M.-M.W., S.-Q.H., Q.S., C.-J.Y., J.-Y.L., X.-H.H., Z.-R.Z.)."},{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), HMU, Harbin, China (M.-M.W., L.-Y.Y., H.-B.J., Y.J., Z.-W.P., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., 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Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Xiao","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell 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First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Hong","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3504-3631","authenticated-orcid":true,"given":"Hao-Tian","family":"Xu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Bi","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, China (M.-M.W., Y.S., Y.Z., Y.-C.Y., Z.-X.H., S.Z., X.W., H.X., M.Y., C.M., B.-W.Z., X.-L.L., J.-Y.C., D.Z., Z.H., M.Z., H.-T.X., X.B., J.-J.M., J.S., C.L., Q.-S.W., J.Z., Y.L., Z.-R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Qi","family":"Han","sequence":"additional","affiliation":[{"name":"Departments of Cardio-Oncology and Pharmacy and Oncological Surgery, Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Heilongjiang Key Laboratory for Metabolic Disorder and Cancer Related Cardiovascular Diseases, China (M.-M.W., S.-Q.H., Q.S., C.-J.Y., J.-Y.L., X.-H.H., 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