title: Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment.
abstract: Immune response to tumors can be successfully oriented for therapeutic purposes, as shown by the clinical efficacy of checkpoint blockade in extending the survival of patients with certain solid and hematologic neoplasms. Nonetheless, numerous patients do not benefit from these new treatments. Tumor-specific CD8(+) T lymphocytes, either endogenously revived by checkpoint interference or adoptively transferred after in vitro expansion and retargeting, can be extremely efficient in controlling metastatic disease but have to overcome a number of restraints imposed by growing tumors. This immune escape relies on a profound modification of the tumor environment, which is rendered less permissive to lymphocyte arrival, persistence, and functional activity. We review here emerging findings on the main negative circuits limiting the efficacy of cancer immunotherapy, as well as novel and conventional approaches that can translate into rational combination therapies.
authors.affiliation: Department of Radiation and Cellular Oncology, The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA. Electronic address: aarina@bsd.uchicago.edu.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Leticia
authors.initials: L
authors.lastname: Corrales
authors.affiliation: Verona University Hospital and Department of Medicine, Verona 37134, Italy. Electronic address: vincenzo.bronte@univr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D059248:Chemoradiotherapy; D003602:Cytotoxicity, Immunologic; D020869:Gene Expression Profiling; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000528:radiation effects
keywords: Cancer; Immunosuppression; Infiltration; MDSC; Microenvironment; TIL