Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.

Details

Serval ID
serval:BIB_69B53EDF0867
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.
Journal
Science Translational Medicine
Author(s)
Kvistborg P., Philips D., Kelderman S., Hageman L., Ottensmeier C., Joseph-Pietras D., Welters M.J., van der Burg S., Kapiteijn E., Michielin O., Romano E., Linnemann C., Speiser D., Blank C., Haanen J.B., Schumacher T.N.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
6
Number
254
Pages
254ra128
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whether treatment amplifies previously induced T cell responses or whether it induces new tumor-specific T cell reactivities. Using a combination ultraviolet (UV)-induced peptide exchange and peptide-major histocompatibility complex (pMHC) combinatorial coding, we monitored immune reactivity against a panel of 145 melanoma-associated epitopes in a cohort of patients receiving anti-CTLA-4 treatment. Comparison of pre- and posttreatment T cell reactivities in peripheral blood mononuclear cell samples of 40 melanoma patients demonstrated that anti-CTLA-4 treatment induces a significant increase in the number of detectable melanoma-specific CD8 T cell responses (P = 0.0009). In striking contrast, the magnitude of both virus-specific and melanoma-specific T cell responses that were already detected before start of therapy remained unaltered by treatment (P = 0.74). The observation that anti-CTLA-4 treatment induces a significant number of newly detected T cell responses-but only infrequently boosts preexisting immune responses-provides strong evidence for anti-CTLA-4 therapy-enhanced T cell priming as a component of the clinical mode of action.
Pubmed
Web of science
Create date
29/09/2014 10:18
Last modification date
20/08/2019 14:24
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