**5. GAGs and Immunological Aspects of Cancer Therapy**

The involvement of glycobiology in cancer and the anti-tumoral immune response can be analyzed at several levels. GAGs are involved in the immune response; they can constitute new biomarkers and offer possibilities to develop new immune-therapy targets.

The interconnection of the immune system and various aspects of tumorigenesis are described in all types of cancers [241,242]. An array of immune cells, mainly from the myeloid lineage, macrophages, and dendritic cells, modulate tumor neoangiogenesis. HA is an essential component of the TME, and its abnormal deposition has been assessed in different tumor types. As HA is one of the modulators of tumor angiogenesis, it can influence various immune cells' physiopathology within the TME. HA-induced effects depend on both its polymer size and its complexes with other molecules. Under healthy conditions, HASs and Hyals are a tightly regulated molecular network that keeps HA ECM levels within physiological limits. When pathological conditions appear, and HA homeostasis is perturbed, the enzymes that regulate its characteristics aid the pro-tumoral processes in TME and induce resistance to therapy [243].

Inflammation and tumorigenesis are intertwined processes [244], and inflammatory mechanisms are involved in both the tumors' initiation and progression. In the continuous communication with the ECM, GAGs regulate the cell/matrix interface and the immunerelated mechanisms [2].
