Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells

Sameena Khan, Deborah J. Burt, Christy Ralph, Fiona C. Thistlethwaite, Robert E. Hawkins, Eyad Elkord

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cytotoxic T Lymphocyte Antigen 4 (CTLA4) blockade has shown antitumor activity against common cancers. However, the exact mechanism of immune mediation by anti-CTLA4 remains to be elucidated. Further understanding of how CTLA4 blockade with tremelimumab mediates immune responses may allow a more effective selection of responsive patients. Our results show that tremelimumab enhanced the proliferative response of T effector cells (Teff) upon TCR stimulation, and abrogated Treg suppressive ability. In the presence of tremelimumab, frequencies of IL-2-secreting CD4+ T cells and IFN-γ-secreting CD4+ and CD8+ T cells were increased in response to polyclonal activation and tumor antigens. Importantly, Treg frequency was not reduced in the presence of tremelimumab, and expanded Tregs in cancer patients treated with tremelimumab expressed FoxP3 with no IL-2 release, confirming them as bona fide Tregs. Taken together, this data indicates that tremelimumab induces immune responses mainly by direct activation of Teff rather than by affecting Tregs.

Original languageEnglish
Pages (from-to)85-96
Number of pages12
JournalClinical Immunology
Volume138
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Fingerprint

CTLA-4 Antigen
Regulatory T-Lymphocytes
Interleukin-2
T-Lymphocytes
Neoplasm Antigens
Patient Selection
Thomsen-Friedenreich antibodies
tremelimumab
Neoplasms

Keywords

  • CTLA4
  • Immune regulation
  • T effector cells
  • T regulatory cells
  • Tremelimumab

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. / Khan, Sameena; Burt, Deborah J.; Ralph, Christy; Thistlethwaite, Fiona C.; Hawkins, Robert E.; Elkord, Eyad.

In: Clinical Immunology, Vol. 138, No. 1, 01.2011, p. 85-96.

Research output: Contribution to journalArticle

Khan, Sameena ; Burt, Deborah J. ; Ralph, Christy ; Thistlethwaite, Fiona C. ; Hawkins, Robert E. ; Elkord, Eyad. / Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. In: Clinical Immunology. 2011 ; Vol. 138, No. 1. pp. 85-96.
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