Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Sci Transl Med. 2014 Sep 17;6(254):254ra128. doi: 10.1126/scitranslmed.3008918.

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

Author information

1
The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. p.kvistborg@nki.nl t.schumacher@nki.nl.
2
The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
3
National Institute for Health Research Southampton Experimental Cancer Medicine Centre and Southampton University Hospitals, Tremona Road, Southampton, Hampshire SO16 6YD, UK.
4
Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
5
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Rue Pierre-Decker 4, 1011 Lausanne, Switzerland.

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.

PMID:
25232180
DOI:
10.1126/scitranslmed.3008918
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center