Chemokines and T Cell Trafficking into Tumors: Strategies to Enhance Recruitment of T Cells into Tumors

Abstract

Chemokines are small proteins used by the cells of the immune system in order to orchestrate their movement in the body during physiological and pathological conditions. Yet they are also expressed in tumors and their metastases. There, they mediate a variety of tumor-specific functions, including the recruitment of different immune cell populations to the tumor site. These cells may have a pro-or anti-tumoral function. Yet the cells mediating the latter are often prevented from infiltrating the tumor mass, due to functional or physical barriers. This is a major obstacle for successful tumor immunotherapy based on cytotoxic T cell administration. Genetic and other pre-clinical studies have provided insights into the mechanisms that regulate these barriers, such as the peri-tumoral fibrotic capsule. Recent novel strategies involving modification of the chemokine receptors expressed in the transferred cytotoxic T cells are providing a possible means of overcoming such obstacles. Integration of such strategies in immunotherapy protocols may hopefully pave the way to a more successful clinical application of T cell immunotherapy.