Tuberculosis following PD-1 blockade for cancer immunotherapy.

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.

journal_name

Sci Transl Med

authors

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

doi

10.1126/scitranslmed.aat2702

subject

Has Abstract

pub_date

2019-01-16 00:00:00

issue

475

eissn

1946-6234

issn

1946-6242

pii

11/475/eaat2702

journal_volume

11

pub_type

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