Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense

Abstract

Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a 'microevolutionary' process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display 'enhanced self' to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein-glycan interactions. A better understanding of tumor 'glycan codes' as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

Adhesion GPCRs in Tumorigenesis

“…In normal smooth and skeletal muscle cells, the non-modified CD97 protein core is present, whereas in their malignant counterparts, i.e., in leiomyosarcoma and rhabdomyosarcoma cells, CD97 is found N-glycosylated [66, 67]. It is well known that glycosylation patterns are modified in cancer [88, 89]; therefore, it is important to determine whether such changes are relevant to the tumorigenic process for each individual aGPCR. N-glycosylation of CD97 is mapped to the adhesive EGF-like domains and is needed for the binding of the interaction partner CD55 [67], which is consistent with CD97 and CD55 often being co-expressed in cancer [53, 54, 90–93].…”

Precision glycocalyx editing as a strategy for cancer immunotherapy

“…The "sialome" is a central axis of immune modulation that has not yet been explored in the context of cancer therapy (15)(16)(17). When sufficiently abundant, glycans terminating in sialic acid residues create a signature of healthy self that suppresses immune activation via several pathways (18).…”

A Phase I Study of the Anti-Idiotype Vaccine Racotumomab in Neuroblastoma and Other Pediatric Refractory Malignancies

“…An immunosuppressive capacity of NeuGc‐gangliosides is postulated as they exhibit the capacity to downmodulate CD4 molecules on the T lymphocyte surface or to inhibit dendritic cell differentiation and maturation in vitro . This tolerance may be altered by active specific immunotherapy …”