Barber DL, Sakai S, Kudchadkar RR, Fling SP, Day TA, Vergara JA, Ashkin D, Cheng JH, Lundgren LM, Raabe VN, Kraft CS, Nieva JJ, Cheever MA, Nghiem PT, Sharon E
Sci Transl Med. 2019 Jan 16;11(475). pii: eaat2702. doi: 10.1126/scitranslmed.aat2702.
View Abstract and Highlights
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.