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

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.

Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma

“…The abundant galectins levels both in TME and peripheral blood have been proposed as prognostic factors and associated to a negative prognosis for oncologic patients [ 130 , 136 ]. Several galectins have been found in both neurons and glial cells and physiologically contribute to CNS development and functions.…”

Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy?

“…Tumor cells weaken the function of immune cells by secreting galectin-1. This induces the tumor microenvironment to shift to the direction of immunosuppression and leads to immune escape of tumor cells ( 95 ). In addition, galectin-1 selectively reduces the viability of Th1 cells and participates in the immunosuppressive microenvironment by promoting the production of Th2 cytokines and the expansion of regulatory T cells ( 96 ).…”

Inhibition of galectins in cancer: Biological challenges for their clinical application

“…Galectins are a family of proteins defined by their Carbohydrate Recognition Domain tumor angiogenesis [reviewed in (19, 20)] and immune escape [reviewed in (7,8,15)]. Consequently, increased galectin production in cancers generally predicts a poor clinical outcome for patients (21-24).…”

“…Expression of galectins is strongly altered in cancer; comprehensive reviews address this point elsewhere ( 8 , 14 , 15 ). Albeit not oncogenic drivers, galectins exacerbate the malignant phenotype ( 16 – 18 ).…”

“…Albeit not oncogenic drivers, galectins exacerbate the malignant phenotype ( 16 – 18 ). Indeed, galectins regulate homotypic and heterotypic aggregation of cancer cells, cancer cell migration and invasion [reviewed in ( 17 )], tumor angiogenesis [reviewed in ( 19 , 20 )] and immune escape [reviewed in ( 7 , 8 , 15 )]. Consequently, increased galectin production in cancers generally predicts a poor clinical outcome for patients ( 21 – 24 ).…”