Galectins in tumour immunity
Dr Gabriel Rabinovich - Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina
Do galectins appear naturally in healthy host cells?
Galectins are involved in as well, galectin 1, the one that we are studying, are particularly over-expressed in tumour cells and their expression correlates with malignancy and with acquisition of a metastatic phenotype. So what we found is that when tumours produce galectin 1 it’s in very high concentrations and it’s in its dimeric form and it’s a glycogen binding protein, it’s a sugar binding protein, so it’s binding to sugars on the surface of T-cells and immune cells and endothelial cells and creates an immunosuppressive microenvironment on these cells.
How does this affect the immune suppressive environment?
What we have found is that secretion of galectin 1 by tumour cells induces apoptosis of T-cells, so it kills T-cells, but it is also promotes tolerogenic dendritic cells, so dendritic cells which are unable to present antigens to T-cells. So this is part of the function of galectins that are related to immunoregulation and immunosuppression but part of the functions of galectins, particularly galectin 1, are related to their ability to create blood vessels. So they have two different functions in modulating immune signalling programmes and in modulating vascular signalling programmes. So we reason that if we block galectin 1 expression then we will increase and unleash T-cell responses to kill the tumour but also we will reduce the number of blood vessels that are generated in the tumour microenvironment.
Have there been clinical trials?
In fact, we have generated some antagonists and some inhibitors and monoclonal antibodies and I think we will move in the next few years to clinical trials and to move to study with patients. But all the work has been done to date with preclinical models.
Is this similar to checkpoint inhibitors?
Checkpoint inhibitors are cell surface associated molecules. For example PD-L1 is expressed on tumour cells and also in macrophages, androgen presenting cells and in the case of CTLA4 it is particularly on T-cells but this is cell-cell surface proteins. In this case galectin 1 is secreted so it’s a soluble protein that accesses a cytokine and it’s secreted at different stages of the cell. So it involves different functions at different stages of cell differentiation.
How can viewers keep up with the latest developments?
You can check our website, Rabinovich Lab, which is my name, Gabriel Rabinovich, and of course you can write me an email to gabirabi.gmail.com
What is your summary message?
In fact, we are really happy and delighted to do collaborations. We are settled in Argentina so it’s quite far away, and we would love to do collaborations with many people from the United States and Europe and we are still doing this collaboration with many people and it has enriched our field a lot. We identified galectin 1 as early as 1991 when I was a student and we started to do this research demonstrating the function in tumour cells, in autoimmune diseases. The mechanisms that were involved and the function in angiogenesis and now we generated this antagonist and agonist of galectins but we would like to integrate this into other fields as well of tumour biology.