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Sci Transl Med. 2019 Jan 16;11(475). pii: eaat2702. doi: 10.1126/scitranslmed.aat2702.

Tuberculosis following PD-1 blockade for cancer immunotherapy.

Author information

1
T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. barberd@niaid.nih.gov sharone@mail.nih.gov.
2
T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
3
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
4
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
5
Cancer Immunotherapy Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
6
Clinical Immunology Group, Infectious Disease Research Institute, Seattle, WA 98102, USA.
7
Division of Infectious Diseases and Global Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
8
Norris Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
9
Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA.
10
Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA 30322, USA.
11
Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
12
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA. barberd@niaid.nih.gov sharone@mail.nih.gov.

Abstract

Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models, Mtb-infected PD-1-/- mice mount exaggerated TH1 responses that drive lethal immunopathology. Multiple cases of tuberculosis during PD-1 blockade have been observed in patients with cancer, but in humans little is understood about Mtb-specific immune responses during checkpoint blockade-associated tuberculosis. Here, we report two more cases. We describe a patient who succumbed to disseminated tuberculosis after PD-1 blockade for treatment of nasopharyngeal carcinoma, and we examine Mtb-specific immune responses in a patient with Merkel cell carcinoma who developed checkpoint blockade-associated tuberculosis and was successfully treated for the infection. After anti-PD-1 administration, interferon-γ-producing Mtb-specific CD4 T cells became more prevalent in the blood, and a tuberculoma developed a few months thereafter. Mtb-specific TH17 cells, CD8 T cells, regulatory T cells, and antibody abundance did not change before the appearance of the granuloma. These results are consistent with the murine model data and suggest that boosting TH1 function with PD-1 blockade may increase the risk or severity of tuberculosis in humans.

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