Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells

Abstract

The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created “sialic acid low” tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing “sialic acid low” tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack.

Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

“…Nevertheless, we observed a relevant growth difference in 2 different models. Previous experiments with B16 melanoma cell lines have also shown similar results, although different approaches were used for the reduction of tumor sialylation (45). Another analysis with hyposialylated methylcholanthrene-induced (MCA-induced) tumors has shown growth inhibition of subcutaneous tumors (46).…”

Effect of cytokine-induced killer cells on immune function in patients with lung cancer

“…Autoimmune disorders in patients lung cancer are demonstrated by reduced levels of CD4 + and CD3 + CD56 + cells, and increased levels of CD8 + cells (25,26). The response of the human immune system against tumors mainly depends on cellular immunity (27). CD3 + T cells are mature T cells, while CD4 + T cells are considered to have a predefined role as Th cells (28).…”

Hallmarks of glycosylation in cancer

“…Growing evidence suggests that interactions between tumour specific glycans and lectins on immune cells are involved in modulating the tumour microenvironment [145]. Glycans regulate various aspects of the immune response and can interfere with the anti-tumour response of the immune system, leading to the emergence of cancer cells resistant to the immune system [11, 146]. This process is mediated by various lectins that bind glycans and regulate immune processes [147, 148].…”