Adoptive T-cell therapy: Optimizing chemokine receptor- mediated homing of T cells in cancer immunotherapy

Abstract

Immunotherapy based on adoptive T-cell transfer provides a promising form of cancer therapy, but often fails to induce long-lasting responses in the great majority of patients. During the past few decades, several strategies for enhancing the efficacy of adoptive T-cell therapy have been developed and introduced into the clinic. These include different maneuvers such as ex vivo expansion of autologous lymphocytes isolated from tumor, manipulating tumor-infiltrating lymphocytes for the expression of tumor-specific T-cell receptors, and genetic manipulation by introducing chimeric antigen receptor followed by expansion and reinfusion into patients. However, one major step that limits the efficacy of this T-cell-based therapy is the failure of sufficient antitumor T cells to efficiently reach the tumor site. Recent studies show intra-tumoral expression of chemokines that may increase immune cell infiltration. This finding reveals the possibility of developing novel strategies aimed at improving T-cell homing to tumors. Such strategies, used alone or in combination with current regime of adoptive T-cell therapies against cancer, may prove to be more efficient and hold great promises in several oncological settings.