title: Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.
abstract: The frontiers of cancer immunotherapy are extending in terms of both the range of cancer types that can potentially be targeted and the types of therapeutics that are in clinical development. The use of adoptive cellular therapy (ACT) and its derivative, chimeric antigen receptor (CAR) T cells, is currently limited to hematological malignancies and immunogenic cancers such as melanoma and renal cell carcinoma. Although ACT utilizing ex vivo expanded tumor-infiltrating lymphocytes (TIL) or engineered CAR/TCR T cells have undergone clinical trials for other solid cancers, their efficacy to date has been limited. This may be due, in part, to the immunosuppressive nature of the tumor microenvironment. The development of novel combination approaches which target the immunosuppressive network engineered by tumors has raised the possibility of using ACT for a broader range of cancers. This review summarizes the potential of such strategies and outlines the clinical relevance of these observations.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia. Electronic address: paula.beavis@petermac.org.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Beavis
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia.
authors.forename: Clare Y
authors.initials: CY
authors.lastname: Slaney
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia; Department of Pathology, University of Melbourne, Parkville, Australia; Department of Immunology, Monash University, Clayton, Australia.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
authors.affiliation: Division of Cancer Surgery, Peter MacCallum Cancer Centre, Australia; Department of Surgery, University of Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Gyorki
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Neeson
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia; Department of Pathology, University of Melbourne, Parkville, Australia; Department of Immunology, Monash University, Clayton, Australia. Electronic address: phil.darcy@petermac.org.
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Darcy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology*; D002470:Cell Survival; D003131:Combined Modality Therapy; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D061025:Costimulatory and Inhibitory T-Cell Receptors; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Adoptive cellular therapy; Cancer; Chimeric antigen receptor; Immunosuppression; Immunotherapy