Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8 <sup>+</sup> regulatory T cells
Alejandro J. Cagnoni, María Laura Giribaldi, Ada G. Blidner, Anabela M. Cutine, Sabrina G. Gatto, Rosa María Morales, Mariana Salatino, Martı́n C. Abba, Diego O. Croci, Karina V. Mariño, Gabriel A. Rabinovich
Abstract
Significance Although immune checkpoint blockade therapies have achieved long-term responses in several malignancies, in colorectal cancer (CRC) patients clinical benefit is observed only in heavily mutated tumors that are mismatch-repair–deficient or have high microsatellite instability. This limitation urges the identification of novel immune escape mechanisms and the design of additional immunotherapeutic modalities. We show that Galectin-1 (Gal-1) confers immune privilege to CRC by increasing the frequency of CD8 + CD122 + PD-1 + regulatory T cells (Tregs) and accentuating their immunosuppressive activity in experimental models. Accordingly, analysis of CRC patient datasets revealed a “poor prognosis signature” characterized by high Gal-1 expression and elevated CD8 + Treg score. Thus, targeting Gal-1/glycan interactions may represent a potential immunotherapeutic modality for treating CRC by recalibrating the CD8 + Treg compartment.