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The glycome’s role in a malignancy

Altered glycosylation in cells could be associated with the malignant transformation in colon cancer.

Colorectal cancer, or CRC, is the leading cause of cancer death worldwide. The disease takes many forms and is difficult to diagnosis and treat. By identifying biomarkers, researchers hope to better understand CRC’s progression and find effective therapies. One clue might be provided by the covalent attachment of complex sugar molecules such as glycans. Researchers have seen that altered glycosylation can be associated with colon cancer becoming malignant.

To investigate this further, Di Wang and researchers at Leiden University Medical Center in the Netherlands analyzed the glycosphingolipid, or GSL, glycans of 22 CRC cell lines using porous graphitized carbon nano–liquid chromatography coupled with electrospray ionization–mass spectrometry.

The team found that GSL expression varies among different cell line classifications: Undifferentiated CRC cell lines were characterized by a high abundance of specific antigens that corresponded to the blood type of the person they were derived from. On the other hand, differentiated CRC cell lines contained prominent GSL glycans such as (sialyl)-LewisA/X and LewisB/Y antigens. By combining glycomics data with transcriptomic analysis, the researchers found a strong correlation between Lewis antigens in CRC cells and increased levels of glycosyltransferase FUT3 and numerous transcription factors, both of which influence colon differentiations. This could explain how GSL glycans can influence differentiation in conditions such as CRC.

This , recently published in the journal Â鶹´«Ã½É«ÇéƬ & Cellular Proteomics, can serve as a resource for future research on biomarkers for CRC and pave the way for further studies.

Where immunopeptidomics is going

Cover by Luciana Giono

, edited by Pierre Thibault and Claude Perreault.

In the 1970s, Baruj Benacarraf and Hugh McDevitt described the regulation of the immune response by the major histocompatibility complex, or MHC, a group of genes that code for proteins found on the surfaces of cells. The MHC locus is the most polymorphic region of the human genome. With this diversity, MHC molecules are able to present a wide distribution of antigen peptides to T cells, which discriminate self and nonself from many of these antigen peptides. Environmental stimuli and proteolytic enzymes in distinct cell organelles shape these antigen peptides’ biogenesis.

The isolation and characterization of these MHC-bound peptides, most commonly using liquid chromatography and mass spectrometry, is called immunopeptidomics. In an  introducing in the journal Â鶹´«Ã½É«ÇéƬ & Cellular Proteomics, Pierre Thibault and Claude Perreault describe this evolving field and recent developments in immunopeptidomic workflows encompassing enrichment and labeling strategies, mass spectrometry acquisition methods, sequencing and allele prediction software. They write that challenges with current methodologies include standardization and sensitivity of the techniques.

With advances in technology, immunopeptidomics provides new opportunities for basic and applied research in immunology. Such improvements especially benefit the field of immuno-oncology, where research can improve the efficacy of immunotherapies, including therapeutic vaccines and bispecific T-cell engagers.