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Tuberculosis following PD-1 blockade for cancer immunotherapy.
- Source :
- Science Translational Medicine; 1/16/2019, Vol. 11 Issue 475, pN.PAG-N.PAG, 1p
- Publication Year :
- 2019
-
Abstract
- Increased Mtb-specific T<subscript>H</subscript>1 responses precede tuberculosis associated with PD-1 blockade. Preaching caution with PD-1 blockade for TB: Scientists are interested in leveraging PD-1 blockade for diseases other than cancer, such as tuberculosis (TB). Barber et al. studied two patients with cancer who developed active TB during PD-1 blockade. Analysis of longitudinal samples available from one of the patients revealed the presence of TB-specific T<subscript>H</subscript>1 cells before presentation of TB. These results are in line with previous work in mouse TB models, which showed that PD-1 deficiency exacerbated disease. This report indicates that PD-1 blockade for treating tuberculosis in humans may instead worsen the disease. 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<superscript>−/−</superscript> mice mount exaggerated T<subscript>H</subscript>1 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 T<subscript>H</subscript>17 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 T<subscript>H</subscript>1 function with PD-1 blockade may increase the risk or severity of tuberculosis in humans. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19466234
- Volume :
- 11
- Issue :
- 475
- Database :
- Complementary Index
- Journal :
- Science Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 134153534
- Full Text :
- https://doi.org/10.1126/scitranslmed.aat2702