title: Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report.
abstract: The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities.
  
  
  
  The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples. The efficacy of high-intensity immunosuppression to reverse graft rejection was explored.
  
  
  
  Endomyocardial biopsy showed acute moderate diffuse cellular rejection with a predominant population of CD3+, CD8+ and CD4+ infiltrating lymphocytes; peripheral blood circulating lymphocytes showed a high frequency of proliferating and activated CD8+ T cells expressing PD-1 compared to a normal control. There was no difference in the activation and proliferation of CD4+ T cells compared to a normal control. Cardiac function improved following high-intensity immunosuppression and patient survived for up to 7 months after discontinuation of nivolumab.
  
  
  
  Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.
authors: Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA. towonik@emory.edu.|Winship Cancer Institute, Emory University, Atlanta, GA, USA. towonik@emory.edu.
authors: Taofeek K
authors: TK
authors: Owonikoko
authors: Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA.
authors: Mukesh
authors: M
authors: Kumar
authors: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors: Shu
authors: S
authors: Yang
authors: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors: Alice O
authors: AO
authors: Kamphorst
authors: Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA.
authors: Rathi N
authors: RN
authors: Pillai
authors: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors: Rama
authors: R
authors: Akondy
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Vivek
authors: V
authors: Nautiyal
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Monica S
authors: MS
authors: Chatwal
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Wendy M
authors: WM
authors: Book
authors: Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: Anurag
authors: A
authors: Sahu
authors: Winship Cancer Institute, Emory University, Atlanta, GA, USA.|Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors: Gabriel L
authors: GL
authors: Sica
authors: Winship Cancer Institute, Emory University, Atlanta, GA, USA.|Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors: Rafi
authors: R
authors: Ahmed
authors: Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA.|Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors: Suresh S
authors: SS
authors: Ramalingam
mesh_terms: D064591:Allografts; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D006084:Graft Rejection / Q000139:chemically induced* / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014181:Transplantation Immunology
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: Allotransplant; Antibody; Cancer; Immunotherapy; PD-1; Rejection