ReportImmunotherapy

Tuberculosis following PD-1 blockade for cancer immunotherapy

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Science Translational Medicine  16 Jan 2019:
Vol. 11, Issue 475, eaat2702
DOI: 10.1126/scitranslmed.aat2702

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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 TH1 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.

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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