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Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance. [ABSTRACT FROM AUTHOR]

Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air-blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients., (© 2024. The Author(s).)