Exacerbation of CMV and Nontuberculous Mycobacterial Infections Following PD-1 Blockade for HIV-Associated Kaposi Sarcoma.

Autor: Anidi IU; Critical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.; T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Sakai S; T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Brooks K; Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Fling SP; Cancer Immunotherapy Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Wagner MJ; Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Lurain K; HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Lindestam Arlehamn CS; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA., Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, California, USA., Knox KS; Department of Internal Medicine, College of Medicine Phoenix, University of Arizona Health Sciences, Phoenix, Arizona, USA., Brenchley JM; Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Uldrick TS; Cancer Immunotherapy Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Sharon E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA., Barber DL; T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2024 Mar 31; Vol. 11 (5), pp. ofae183. Date of Electronic Publication: 2024 Mar 31 (Print Publication: 2024).
DOI: 10.1093/ofid/ofae183
Abstrakt: Blockade of the co-inhibitory receptor PD-1 enhances antitumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here, we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti-PD-1 therapy for Kaposi sarcoma in people with HIV well-controlled on antiretroviral therapy. Less than a week after receiving the first dose of anti-PD-1 antibody (pembrolizumab), he presented with severe abdominal pain associated with sudden exacerbations of preexisting cytomegalovirus (CMV) enteritis and nontuberculous mycobacterial mesenteric lymphadenitis. Plasma biomarkers of gastrointestinal tract damage were highly elevated compared with healthy controls, consistent with HIV-associated loss of gut epithelial barrier integrity. Moreover, CMV-specific CD8 T cells expressed high levels of PD-1, and 7 days following PD-1 blockade, there was an increase in the frequency of activated CD38 + Ki67 + CMV-specific CD8 T cells. This case highlights the potential for PD-1 blockade to drive rapid exacerbations of inflammatory symptoms when administered to individuals harboring multiple unresolved infections.
Competing Interests: Potential conflicts of interest. D. L. B. is listed as an inventor on patents related to PD-1 inhibition. M. J. W. has received honoraria from Charles River Associates for work supported by Boehringer-Ingelheim, and consulting fees for scientific advisory board participation from PharmaEssentia, Deciphera, Adaptimmune, Epizyme, and Aadi. T. S. U. is an employee of Regeneron Pharmaceuticals. He is listed as an inventor on US Patent 10,001,483 B2 for methods of treating KSHV-induced lymphoma using immune modulatory compounds and uses of biomarkers and Patent Application 18/310,649 for KSHV oncoprotein antigens and epitopes for expanding antigen specific T cells. K. L. receives research funding through CRADAs with the NCI from Merck, EMD-Serrono, Eli Lilly, Bristol Myers Squibb, Lentigen, and CTI BioPharma.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
Databáze: MEDLINE
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