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Aberrant O-glycosylation truncates O-glycans and is known to be closely associated with colorectal cancer (CRC), a major gastrointestinal tumor. CD44 is one of the highly post-transcriptionally modified O-glycoproteins participating in a series of physiological and pathobiological processes. In this research, we aimed to investigate whether CD44 expression in cells and exosomes can be influenced by disruption of Core 1-mediated O-glycosylation. Exosomes derived from LS174T and LSC human colon cancer cell lines were isolated from cell culture supernatant and pulled down using tetraspanin-specific antibody CD63 immunoaffinity magnetic beads. Identifications have been performed via transmission electron microscopy (TEM) and flow cytometry. CD63 immunoaffinity-purified exosomes are examined for CD44 expression by flow cytometric analyses. The percentages of CD44 in exosomes derived from abnormally O-glycosylated cells are significantly higher compared with those derived from normal ones, however, which is surprisingly contrary to the cellular expression levels of CD44. The secretion of truncated glycoproteins to the extracellular environment via microvesicles may be most likely its underlying mechanism. CD44 in exosomes might be a potential biomarker of aberrant O-glycosylation. This is the first study indicating that aberrant O-glycosylation can affect expression or delivery of O-glycoproteins via exosomes, which provides us some new sights in therapeutic strategies for human colon cancer. • Aberrant Core 1-mediated O-glycosylation down-regulates intracellular CD44 protein expression while up-regulates its exosomal expression. • Complementation with wtCosmc restores abnormal O-glycosylation, thereby corrects its effects on CD44 both in cells and exosomes. • Truncated CD44 is released to the extracellular environment via exosomes. [ABSTRACT FROM AUTHOR]

• IFNAR1 expression in CD4+ and CD8+ T cells is higher in CRC. • Peripheral blood CD4+ T IFNAR1 levels positively associate with TME CD8+ T cell infiltration. • CD8+ T IFNAR1 expressions were negative associated with plasma IL-2, IFN-γ, and TNFα. • IFNAR1 levels in peripheral blood CD8+ T negatively associate with chemosensitivity. IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4+ and CD8+ T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8+ T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4+ T cells was positively associated with TME infiltrated levels of CD8+ T cells. The levels of CD8+ T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4+ and CD8+ T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response. [ABSTRACT FROM AUTHOR]