Abstract
Galectins are small proteins with pleiotropic functions, which depend on both their lectin (glycan recognition) and non-lectin (recognition of other biomolecules besides glycans) interactions. Currently, 15 members of this family have been described in mammals, each with its structural and ligand recognition particularities. The galectin/ligand interaction translates into a plethora of biological functions that are particular for each cell/tissue type. In this sense, the cells of the immune system are highly sensitive to the action of these small and essential proteins. While galectins play central roles in tumor progression, they are also excellent negative regulators (checkpoints) of the immune cell functions, participating in the creation of a microenvironment that promotes tumor escape. This review aims to give an updated view on how galectins control the tumor’s immune attack depending on the tumor microenvironment, because determining which galectins are essential and the role they play will help to develop future clinical trials and benefit patients with incurable cancer.
Highlights
Worldwide, cancer is a major public health problem
The active role of the immune system controlling tumors is supported by clinical observations that correlate spontaneous tumor regression with autoimmunity after transplants, where the development of cancer is much more frequent than in healthy subjects B[2io,m3]o.leMculoesre20o2v0e, 1r0,t7h5e0 active role of the immune system controlling tumors is supported by cli2noifc2a4l observations that correlate spontaneous tumor regression with autoimmunity
It is interesting to highlight that, along with the axis PD-1/PD-L1 y CTLA-4/B7, these negative ICPs act on various stages of the anti-tumor response, including activation and proliferation in secondary lymphoid tissues, lymphocyte trafficking to sites of antigen expression, the execution of direct effector functions, the provision of help for immune cells, the metabolic control at the clonal expansion and effector phases, the induction of a deactivated/exhausted state in lymphocytes, the functional promotion of regulatory T cells, the activation of innate cells that has an indirect effect on adaptive immune responses, and the regulation of antibody production by B lymphocytes
Summary
Cancer is a major public health problem. It has become the leading cause of death in developed countries, while it shows a continuous progression in developing countries [1]. It is interesting to highlight that, along with the axis PD-1/PD-L1 y CTLA-4/B7, these negative ICPs act on various stages of the anti-tumor response, including activation and proliferation in secondary lymphoid tissues, lymphocyte trafficking to sites of antigen expression, the execution of direct effector functions, the provision of help for immune cells (through cytokines and membrane ligands), the metabolic control at the clonal expansion and effector phases, the induction of a deactivated/exhausted state in lymphocytes, the functional promotion of regulatory T cells, the activation of innate cells that has an indirect effect on adaptive immune responses, and the regulation of antibody production by B lymphocytes Most of these actions are performed through receptor-mediated intracellular signaling in lymphocytes. We will analyze the main clinical trial results highlighting the idea that co-targeting galectins in combination with other immunotherapy (e.g., ICP targeting and/or therapeutic vaccination) may improve and solve several cases and benefit cancer patients
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