The role of Galectin-3 in the tumor microenvironment


Impact of Gal-3 within the TME. Gal-3 is secreted by the tumor cells as monomers, which can form pentamers and bind substrates. The arrows indicate the influence of extracellular Gal-3 on various cell subsets. Gal-3 secreted by tumor cells: 1) polarizes M1 macrophages to M2 macrophages and 2) suppresses CD4 and/or CD8 T cells. Gal-3 secreted by M2 macrophages: 3) binds tumor cells to promote tumor progression/metastasis and 4) suppresses T cells. (Source: Farhad et al., 2020)

Galectin-3 (gal-3), member of the galectin family, is a potential biomarker and therapeutic target in numerous types of cancer. Lectins family members in animals have been implicated in a plethora of cellular processes like: adhesion, migration, survival, death and differentiation. As with the other family members, gal-3 is ubiquitously expressed and is specifically binds β-galactose-containing-glucoconjugates through a specific region named carbohydrate carbohydrate-recognition-binding domain (CRDs). It is well documented that gal-3, produced by tumor cells or immune cells such as M2 macrophages, could have a pro-tumoral activity and participate to tumoral escape from immune responses. In this review, the authors underlying potential immunosuppressive effect of gal-3 through his modulation of lymphocytes and macrophages activity, specifically in the prostate and lung cancer.

Depending on its location, extracellular or intracellular, gal-3 can show pro-or anti apoptotic effect on lymphocytes. Extracellular gal-3 induce thymocytes and T lymphocytes apoptosis due to the stimulation of CD45 or CD71, while intracellular gal-3 inhibit this death process by binding to bcl-2 protein. Gal-3 has also shown an ability to down regulate TCR expression and INF-γ secretion of both CD4 and CD8 T cells. On other hand, Gal-3 can turn classical M1 macrophages into immunosuppressive M2 macrophages.

Despite the known immunosuppressive effect of gal-3 in the tumor microenvironment, its expression is negatively correlated with prostate cancer progression while in non-small Lung cell cancer, high gal-3 expression is associated with metastasis.

The overwhelming evidence of Gal-3 involvement in boosting tumor growth, metastasis, and immune suppression has made Gal-3 an exciting target for cancer immunotherapy. Gal-3 inhibitors, such as GRMD-02 and GCS-100, used alone or in combination with existing immunotherapies have shown promising results in preclinical and clinical trials.

Journal Article: Farhad et al., 2018. The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment. Oncoimmunology

Summary by Doudou Georges Massar Niang

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation