Role Of Sialyltransferases And Sialidases On Galectin-1-Driven Resistance To Immunotherapy: A Bioinformatic Approach

MERLO, JP.; SCHEIDEGGER, MA.; MAHMOUD, YD.; MARIÑO, KV.; DALOTTO-MORENO, T.; RABINOVICH, GA.

Congreso; Reunion Anual de Biociencias 2022; 2022

Objectives. In this study we aimed to explore, using a bioinformatic approach, the role of sialyltransferases ST3GAL1 and ST6GAL1 as well as the NEU1-4 sialidases in resistance to immunotherapy. Materials and Methods. Publicly available single-cell transcriptomics of tumour samples from melanoma patients treated with immunotherapy was analysed using Seurat package v4.0.6 and R software v4.2.0. Background and Results. Galectin-1 (Gal1) has emerged as a critical mediator of resistance to different anti-cancer therapies, including immunotherapy and anti-angiogenic therapies. Gal1 induces apoptosis of fully activated Th1 and Th17 cells; confers tolerogenic potential to dendritic cells and favours M2 polarization of macrophages. Gal1 also confers resistance to anti-VEGF therapies through VEGFR2 binding on endothelial cells and inducing angiogenesis. Since Gal1 binding is inhibited by terminal α2-6-sialylation of protein receptors, we focused on sialyltransferases, which add terminal sialic acid, and on neuraminidases, which can hydrolyse it. Using publicly available transcriptomics data from melanoma patients, we found that cytotoxic and exhausted CD8+ T lymphocytes of non-responding patients showed a decreased expression of ST6GAL1 mRNA compared to responding patients after treatment (p