Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia

Nona Janikashvili, Collin J. LaCasse, Claire Larmonier, Malika Trad, Amanda Herrell, Sara Bustamante, Bernard Bonnotte, Michael Har-Noy, Nicolas Larmonier, Emmanuel Katsanis

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3+ Tregs from naive CD4 +CD25-FoxP3- T cells by an interferon-γ- dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.

Original languageEnglish (US)
Pages (from-to)1555-1564
Number of pages10
JournalBlood
Volume117
Issue number5
DOIs
StatePublished - Feb 3 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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