Regulation of CTL Infiltration Within the Tumor Microenvironment

The tumor microenvironment consists of a complex milieu of cells and factors that maintain equilibrium between tumor progression and destruction. Characterization of the immune contexture in primary tumors has consistently shown that T lymphocytes are an integral predictor of improved clinical outcome. This is notably true in colorectal carcinoma where high densities of cytotoxic or memory T lymphocytes in the invasive margin and the center of the primary tumor predict better patient survival, a measure termed Immunoscore. Since a high Immunoscore and pre-existing adaptive immune response are significantly correlated with improved clinical outcome, it is essential to understand the mechanisms underlying functional T lymphocyte infiltration into the tumor. The ability of cytolytic and memory T lymphocytes to migrate into tumors is regulated by multiple strategies including T lymphocyte help, homing factors, cytokines, tumor genotype, angiogenesis, lymphangiogenesis, and neurological signals. This chapter will discuss the predominant factors that mediate T-lymphocyte infiltration into tumors and how analysis of these biomarkers determine patients' disease-related survival and predicts response to cancer therapy.