Selective inhibition of low-affinity memory CD8(+) T cells by corticosteroids Journal Article

   


Authors: Tokunaga, A.; Sugiyama, D.; Maeda, Y.; Warner, A. B.; Panageas, K. S.; Ito, S.; Togashi, Y.; Sakai, C.; Wolchok, J. D.; Nishikawa, H.
Article Title: Selective inhibition of low-affinity memory CD8(+) T cells by corticosteroids
Abstract: Patients treated with immune checkpoint blockade (ICB) sometimes experience immune-related adverse events (irAEs), requiring immuno-suppressive drugs such as corticosteroids despite the possibility that immunosuppression may impair the antitumor effects of ICB. Here, we address the dilemma of using corticosteroids for the treatment of irAEs induced by ICB. ICB augments neoantigen-specific CD8+ T cell responses, resulting in tumor regression. In our model, simultaneous, but not late, administration of corticosteroids impaired antitumor responses with reduction of CD8+ T cell proliferation. Secondary challenge using tumors with/without the neoantigen showed selective progression in tumors lacking the neoantigen when corticosteroids were administered. Corticosteroids decreased low- but not high-affinity memory T cells by suppressing fatty acid metabolism essential for memory T cells. In a small cohort of human melanoma patients, overall survival was shorter after treatment with CTLA-4 blockade in patients who received early corticosteroids or had low tumor mutation burden. Together, low-affinity memory T cells are dominantly suppressed by corticosteroids, necessitating careful and thoughtful corticosteroid use. © 2019 Tokunaga et al.
Journal Title: Journal of Experimental Medicine
Volume: 216
Issue: 12
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2019-12-02
Start Page: 2701
End Page: 2713
Language: English
DOI: 10.1084/jem.20190738
PUBMED: 31537643
PROVIDER: scopus
PMCID: PMC6888983
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075956675&doi=10.1084%2fjem.20190738&partnerID=40&md5=aa12ec458926575173fb2676783ee7df
Notes: Article -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    905 Wolchok
  2. Katherine S Panageas
    517 Panageas
  3. Allison Betof Warner
    76 Betof Warner
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