Enhancing tumor T cell infiltration to enable cancer immunotherapy

Cancer immunotherapy has changed the treatment landscape for cancer patients, especially for those with metastatic spread. While the immunotherapeutic armamentarium is constantly growing, as exemplified by approved compounds, clinical outcome remains variable both within and across entities. A sufficient infiltration into the tumor microenvironment and successful activation of effector T lymphocytes against tumor cells have been identified as predictors for responses to T cell-based immunotherapies. However, tumor cells have developed a variety of mechanisms to reduce T cell homing and access to the tumor tissue to prevent activity of anticancer immunity. As a consequence, investigations have interrogated strategies to improve the efficacy of cancer immunotherapies by enhancing T cell infiltration into tumor tissues. In this review, we summarize mechanisms of how tumor tissue shapes immune suppressive microenvironment to prevent T cell access to the tumor site. We focus on current strategies to improve cancer immunotherapies through enhancing T cell infiltration.