Targeting the tumor microenvironment to enhance antitumor immune responses

// Kevin Van der Jeught 1 , Lukasz Bialkowski 1 , Lidia Daszkiewicz 1 , Katrijn Broos 1 , Cleo Goyvaerts 1 , Dries Renmans 1 , Sandra Van Lint 1 , Carlo Heirman 1 , Kris Thielemans 1 and Karine Breckpot 1 1 Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium Correspondence: Karine Breckpot, email: // Keywords : Intratumoral, Immunotherapy, Tumor microenvironment, Immunomodulation, Vaccination Received : November 18, 2014 Accepted : December 24, 2014 Published : December 26, 2014 Abstract The identification of tumor-specific antigens and the immune responses directed against them has instigated the development of therapies to enhance antitumor immune responses. Most of these cancer immunotherapies are administered systemically rather than directly to tumors. Nonetheless, numerous studies have demonstrated that intratumoral therapy is an attractive approach, both for immunization and immunomodulation purposes. Injection, recruitment and/or activation of antigen-presenting cells in the tumor nest have been extensively studied as strategies to cross-prime immune responses. Moreover, delivery of stimulatory cytokines, blockade of inhibitory cytokines and immune checkpoint blockade have been explored to restore immunological fitness at the tumor site. These tumor-targeted therapies have the potential to induce systemic immunity without the toxicity that is often associated with systemic treatments. We review the most promising intratumoral immunotherapies, how these affect systemic antitumor immunity such that disseminated tumor cells are eliminated, and which approaches have been proven successful in animal models and patients.