Abstract SY28-01: Immunotherapy in combination with neoadjuvant therapy and immune-related adverse events

Abstract

Abstract Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer treatment. Although immunotherapy has begun to have success in advanced cancer treatment, its scheduling and efficacy with conventional therapies, such as surgery, has not been systematically examined. Here, we have used two models of spontaneously metastatic breast cancers in mice to compare the therapeutic power of neoadjuvant versus adjuvant immunotherapies in the context of primary tumor resection. Therapies, including Treg depletion, anti-PD-1 or anti-PD1/anti-CD137 combinations were evaluated. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood sampling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. New combination immunotherapies are displaying both efficacy and immune-related adverse events (irAEs) in humans. Prolonged T regulatory cell (Treg) depletion in tumor bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of antitumor responses and severity of irAEs that can occur in ipilimumab/nivolumab treated patients, while transient Treg depletion and anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune tolerance threshold and allowing irAEs to be more easily provoked following treatment with additional immunomodulatory antibodies. This platform has been used to compare a number of promising immunotherapies. Citation Format: Mark J. Smyth, Jing Liu, Stephen J. Blake, Michele WL Teng. Immunotherapy in combination with neoadjuvant therapy and immune-related adverse events. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY28-01.