title: Targeting the tumor microenvironment to enhance antitumor immune responses.
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.
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Kevin
authors: K
authors: Van der Jeught
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Lukasz
authors: L
authors: Bialkowski
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Lidia
authors: L
authors: Daszkiewicz
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Katrijn
authors: K
authors: Broos
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Cleo
authors: C
authors: Goyvaerts
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Dries
authors: D
authors: Renmans
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Sandra
authors: S
authors: Van Lint
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Carlo
authors: C
authors: Heirman
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Kris
authors: K
authors: Thielemans
authors: Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan, Jette, Belgium.
authors: Karine
authors: K
authors: Breckpot
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D059016:Tumor Microenvironment / Q000276:immunology*