title: Regulation of cytotoxic T-Lymphocyte trafficking to tumors by chemoattractants: implications for immunotherapy.
abstract: Cancer immunotherapy has recently emerged as an important treatment modality. FDA approval of provenge, ipilimumab and pembrolizumab has started to deliver on the long awaited promise of cancer immunotherapy. Many new modalities of immunotherapies targeting cytotoxic T lymphocytes (CTLs) responses, such as adoptive cell therapies and vaccines, are in advanced clinical trials. In all these immunotherapies, migration of CTLs to the tumor site is a critical step for achieving therapeutic efficacy. However, inefficient infiltration of activated CTLs into established tumors is increasingly being recognized as one of the major hurdles limiting efficacy. Mechanisms that control migration of CTLs to tumors are poorly defined. In this review, the authors discuss the chemoattractants and their receptors that have been implicated in endogenous- or immunotherapy-induced CTL recruitment to tumors and the potential for targeting these pathways for therapeutic efficacy.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville Health Sciences, Louisville, KY 40202, USA.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Zinal S
authors.initials: ZS
authors.lastname: Chheda
authors.forename: Venkatakrishna R
authors.initials: VR
authors.lastname: Jala
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
mesh_terms: D002465:Cell Movement; D002630:Chemotactic Factors / Q000378:metabolism*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology
chemical_list: D002630:Chemotactic Factors
keywords: BLT1; CD8+ T cells; CTL migration; CXCR3; anti-tumor immunity; cancer; cancer immune surveillance; chemokine receptors; chemokines; leukotriene B4