Angiostasis as a way to improve immunotherapy.
Tumours express tumour-associated antigens that are recognised as self-antigens precluding the induction of effective anti-tumour immune responses. Inflammatory conditions which facilitate appropriate antigen presentation and reduce the immuno-suppressive micro-milieu may break tolerance. However, tumours have evolved mechanisms to escape cytotoxic T-cell attack by expressing inhibitory molecules on their surface, secreting suppressive factors, attracting regulatory T cells to the tumour environment or downregulating MHC molecules. Induction of angiogenesis by tumours may represent another mechanism by which tumours escape from immune attack. It provides an anti-inflammatory milieu that will prevent appropriate activation and maturation of antigen presenting cells, allow tumours to secrete suppressive factors and inhibit expression of tumour endothelial adhesion receptors, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin, needed for appropriate interactions with immune cells. Inhibition of angiogenesis may, apart from its direct detrimental effects on the tumour, reverse these processes and contribute to anti-tumour immune reactivity. Without trying to give a complete overview of the field, this paper reviews insights on angiogenesis inhibition in relation to tumour immune responsiveness, mainly based on the Maastricht-Amsterdam experience. This review adds to the hypothesis of improvement of immuno-directed therapies for cancer by angiostasis.
Griffioen
Arjan W
AW
Angiogenesis Laboratory, Dept. of Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. aw.griffioen@vumc.nl
Vyth-Dreese
Florry A
FA
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007157:Immunologic Surveillance; D007167:Immunotherapy; D009369:Neoplasms / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009426:Netherlands; D019139:Tumor Escape
D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules