Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity.
Cancer cells express self-antigens that are weakly recognized by the immune system. Even though responses against autologous cells are difficult to induce, the immune system is still able to mount a response against cancer. The discovery of the molecular identity of antigens that are recognized by the immune system of melanoma patients has led to the elucidation of tumor immunity at a cellular and molecular level. Multiple pathways in both the priming and effector phases of melanoma rejection have been described. Animal models' active immunotherapies for melanoma show a requirement for the cellular compartment of the immune system in the priming phase, primarily CD4+T cells. More diverse elements are required for the effector phase, including components from the innate immune system (macrophages, complement and/or natural killer cells) and from the adaptive immune system (CD8+T cells and B cells). Minor differences in amino-acid sequences of antigens must determine the particular mechanisms involved in tumor rejection. Since the immune system contains T and B cells that recognize and reject autologous cells, a consequence of tumor immunity is potential autoimmunity. There are distinct pathways for tumor immunity and autoimmunity. The requirements for autoimmunity at the priming phase seem to be CD4+/IFN-gamma dependent while the effector mechanisms are alternative and redundant. Vitiligo (autoimmune hypopigmentation) can be mediated by T cells, FcgammaR+macrophages and/or complement.
Ramirez-Montagut
Teresa
T
Memorial Sloan-Kettering Cancer Center and the Weill Graduate School of Medical Sciences of Cornell University, 1275 York Avenue, New York, NY 10021, USA.
Turk
Mary Jo
MJ
Wolchok
Jedd D
JD
Guevara-Patino
José A
JA
Houghton
Alan N
AN
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000502:physiology; D015551:Autoimmunity / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005854:Germ Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D019139:Tumor Escape
D000906:Antibodies; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm