title: Combination cancer immunotherapy and new immunomodulatory targets.
abstract: Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA. [2] Division of Haematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. [3].
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mahoney
authors.affiliation: 1] SugarCone Biotech, Holliston, Massachusetts 01746, USA. [2] Videre Biotherapeutics, Watertown, Massachusetts 02472, USA. [3].
authors.forename: Paul D
authors.initials: PD
authors.lastname: Rennert
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor