Unraveling How Tumor-Derived Galectins Contribute to Anti-Cancer Immunity Failure

SIMPLE SUMMARY: This review compiles our current knowledge of one of the main pathways activated by tumors to escape immune attack. Indeed, it integrates the current understanding of how tumor-derived circulating galectins affect the elicitation of effective anti-tumor immunity. It focuses on several relevant topics: which are the main galectins produced by tumors, how soluble galectins circulate throughout biological liquids (taking a body-settled gradient concentration into account), the conditions required for the galectins’ functions to be accomplished at the tumor and tumor-distant sites, and how the physicochemical properties of the microenvironment in each tissue determine their functions. These are no mere semantic definitions as they define which functions can be performed in said tissues instead. Finally, we discuss the promising future of galectins as targets in cancer immunotherapy and some outstanding questions in the field. ABSTRACT: Current data indicates that anti-tumor T cell-mediated immunity correlates with a better prognosis in cancer patients. However, it has widely been demonstrated that tumor cells negatively manage immune attack by activating several immune-suppressive mechanisms. It is, therefore, essential to fully understand how lymphocytes are activated in a tumor microenvironment and, above all, how to prevent these cells from becoming dysfunctional. Tumors produce galectins-1, -3, -7, -8, and -9 as one of the major molecular mechanisms to evade immune control of tumor development. These galectins impact different steps in the establishment of the anti-tumor immune responses. Here, we carry out a critical dissection on the mechanisms through which tumor-derived galectins can influence the production and the functionality of anti-tumor T lymphocytes. This knowledge may help us design more effective immunotherapies to treat human cancers.