Cytotoxic T lymphocyte migration and effector function in the tumor microenvironment

Abstract

Immunological control of cancer lesions requires local uptake of tumor-specific antigen followed by the activation and expansion of tumor specific cytotoxic T-lymphocytes (CTL). An efficient effector phase further depends upon the entry of activated CTL into the tumor microenvironment and scanning of tumor tissue, which leads to direct interaction of the CTL with target cells followed by apoptosis induction and shrinkage of the tumor lesion. Whereas the antigens and pathways that lead to efficient activation of tumor-specific CTL are well established, the local mechanisms that enable efficient - or deficient - CTL function in the tumor tissue are poorly understood. Firstly, effector T lymphocytes need to be mobile to reach the tumor lesion. Next, they must physically interact with and scan tumor cells for antigenic MHC/peptide complexes. Lastly, CTLs must undergo activation and functional conjugation with target cells to induce apoptosis either by the release of perforins or the engagement of Fas/FasL. All these steps of effector function are interdependent and require the amoeboid migration of CTL through tissue to reach, engage with and leave encountered cells.