Tuberculosis following PD-1 blockade for cancer immunotherapy
Top Cited Papers
- 16 January 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 11 (475)
- https://doi.org/10.1126/scitranslmed.aat2702
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.Keywords
Funding Information
- National Cancer Institute
- National Cancer Institute (5UM1CA154967)
- National Cancer Institute (P30CA014089)
- Merck
- Merck (CITN-09/KEYNOTE-017 trial)
- NIAID Intramural Research Program
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