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.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID 30651320 [ - in process]
https://www.ncbi.nlm.nih.gov/m/pubmed/30651320/
Tuberculosis following PD-1 blockade for cancer immunotherapy.
Re: Tuberculosis following PD-1 blockade for cancer immunotherapy.
Tuberculosis following PD-1 blockade for cancer immunotherapy
https://merkelcell.org/wp-content/uploa ... deImtx.pdf
https://merkelcell.org/wp-content/uploa ... deImtx.pdf
Debbie
Re: Tuberculosis following PD-1 blockade for cancer immunotherapy.
My thought and purpose is to educate of the possibility not to scare anyone .
It looks like the reports of TB being induced during immunotherapy , is being found in older patients ?
https://www.google.com/amp/s/www.the-sc ... -65636/amp
It looks like the reports of TB being induced during immunotherapy , is being found in older patients ?
https://www.google.com/amp/s/www.the-sc ... -65636/amp
Debbie
Re: Tuberculosis following PD-1 blockade for cancer immunotherapy.
Deb, any meaningful evidence based information from the credible medical publications has a right to be posted here, if relevant. Regardless how scary it is.
re. subject - probably there is a difference in how immune system operates in younger and older folks, hard to say. it is true, that when evaluating the risks, the proper risk group should be identified if possible.
re. subject - probably there is a difference in how immune system operates in younger and older folks, hard to say. it is true, that when evaluating the risks, the proper risk group should be identified if possible.
Olga