Taofeek K Owonikoko1,2, Mukesh Kumar3, Shu Yang4, Alice O Kamphorst4, Rathi N Pillai3, Rama Akondy4, Vivek Nautiyal5, Monica S Chatwal5, Wendy M Book5, Anurag Sahu5, Gabriel L Sica6,7, Rafi Ahmed6,4, Suresh S Ramalingam3,6. 1. 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. 2. Winship Cancer Institute, Emory University, Atlanta, GA, USA. towonik@emory.edu. 3. Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA. 4. Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. 5. Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 6. Winship Cancer Institute, Emory University, Atlanta, GA, USA. 7. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.
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