Abstract 4054: Mast cells contribute to T cell tolerance against prostate cancer- associated antigens favoring tumor growth

Treatments for hormone refractory and metastatic prostate cancer (PC) still remain palliative. Also tumor specific vaccinations when tested in the clinical setting showed results lower than expected. A major limitation to active immunotherapy relies on mechanisms of tolerance adopted by the tumor. Indeed, an immunosuppressive environment is established in PC patients, as well as in the TRAMP mouse model of PC, in which peripheral T cell tolerance to the tumor-associated antigen Tag is acquired early during neoplastic transformation, with mechanisms that still need to be fully clarified.Mast cells (MCs) have been described to mediate immunological tolerance in transplantation and in several disease models, including cancer. We have demonstrated their involvement in early stage of PC development. Therefore, we investigated whether immunosuppression is part of their supporting adenocarcinoma outgrowth in TRAMP mice.We crossed TRAMP mice with KitWsh mice, genetically lacking MCs, and followed tumor growth and Tag-specific CD8+ T cells response after immunization, measured as in vivo lytic activity or ex vivo cytokine production.MCs depletion restrained adenocarcinoma growth in about 70% of mice that at 30 weeks of age only showed evidences of intraepithelial neoplasia or local in situ well-differentiated adenocarcinoma. These lesions were much different from those raised in MCs-sufficient age-matched TRAMP counterparts that developed poor-differentiated multifocal invasive carcin...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research