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RESEARCH PRODUCT

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

Nicolas LarmonierBernard BonnotteMalika TradAmanda HerrellMichael Har-noyNona JanikashviliSara BustamanteCollin J. LacasseClaire B. LarmonierEmmanuel Katsanis

subject

Cell Extractsmedicine.medical_treatmentBlotting WesternImmunologyMice NudeEnzyme-Linked Immunosorbent Assaychemical and pharmacologic phenomenaMice SCIDBiologyCancer VaccinesT-Lymphocytes RegulatoryBiochemistryInterferon-gammaMiceLymphocytes Tumor-InfiltratingImmune systemCancer immunotherapyAntigenTumor Cells CulturedmedicineAnimalsInterferon gammaIL-2 receptorImmunobiologyMice Inbred BALB CLeukemia ExperimentalFOXP3hemic and immune systemsForkhead Transcription FactorsDendritic CellsT-Lymphocytes Helper-InducerCell BiologyHematologyT lymphocyteFlow Cytometrymedicine.diseaseMice Inbred C57BLLeukemiaImmunologyImmunologic MemoryMolecular ChaperonesT-Lymphocytes Cytotoxicmedicine.drug

description

AbstractTherapeutic 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.

yearjournalcountryeditionlanguage
2011-02-03Blood
https://doi.org/10.1182/blood-2010-06-288621