title: Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells.
abstract: It has become evident that tumor-induced immuno-suppressive factors in the tumor microenvironment play a major role in suppressing normal functions of effector T cells. These factors serve as hurdles that limit the therapeutic potential of cancer immunotherapies. This review focuses on illustrating the molecular mechanisms of immunosuppression in the tumor microenvironment, including evasion of T-cell recognition, interference with T-cell trafficking, metabolism, and functions, induction of resistance to T-cell killing, and apoptosis of T cells. A better understanding of these mechanisms may help in the development of strategies to enhance the effectiveness of cancer immunotherapies.
authors.affiliation: Department of Oncology; The Johns Hopkins University School of Medicine ; Baltimore, MD USA.
authors.forename: Annie A
authors.initials: AA
authors.lastname: Wu
authors.affiliation: School of Medicine; University of Maryland ; Baltimore, MD USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Drake
authors.affiliation: College of Medicine; National Taiwan University ; Taipei, Taiwan.
authors.forename: Huai-Shiuan
authors.initials: HS
authors.lastname: Huang
authors.affiliation: College of Medicine; National Taiwan University ; Taipei, Taiwan.
authors.forename: ShihChi
authors.initials: S
authors.lastname: Chiu
authors.affiliation: Department of Oncology; The Johns Hopkins University School of Medicine ; Baltimore, MD USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
keywords: 1MT, 1-methyltryptophan; COX2, cyclooxygenase-2; GM-CSF, granulocyte macrophage colony-stimulating factor; GPI, glycosylphosphatidylinositol; Gal1, galectin-1; HDACi, histone deacetylase inhibitor; HLA, human leukocyte antigen; IDO, indoleamine-2,3- dioxygenase; IL-10, interleukin-10; IMC, immature myeloid cell; MDSC, myeloid-derived suppressor cells; MHC, major histocompatibility; MICA, MHC class I related molecule A; MICB, MHC class I related molecule B; NO, nitric oxide; PARP, poly ADP-ribose polymerase; PD-1, program death receptor-1; PD-L1, programmed death ligand 1; PGE2, prostaglandin E2; RCAS1, receptor-binding cancer antigen expressed on Siso cells 1; RCC, renal cell carcinoma; SOCS, suppressor of cytokine signaling; STAT3, signal transducer and activator of transcription 3; SVV, survivin; T cells; TCR, T-cell receptor; TGF-β, transforming growth factor β; TRAIL, TNF-related apoptosis-inducing ligand; VCAM-1, vascular cell adhesion molecule-1; XIAP, X-linked inhibitor of apoptosis protein; iNOS, inducible nitric-oxide synthase; immunosuppression; immunosuppressive factors; immunotherapy; tumor microenvironment