Regulation of cytotoxic T-Lymphocyte trafficking to tumors by chemoattractants: implications for immunotherapy

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.