Tumor immunity via homeostatic T cell proliferation: mechanistic aspects and clinical perspectives.
Efforts to develop effective anti-tumor immunotherapies are hampered by the difficulty of overcoming tolerance against tumor antigens, which in most instances are normal gene products that are over-expressed, preferentially expressed or re-expressed in cancer cells. Considering that lymphopenia-induced homeostatic T cell proliferation is mediated by self-peptide/MHC recognition and that the expanded cells acquire some effector functions, we hypothesized that this process could be used to break tolerance against tumor antigens. Studies by us and others in several mouse models demonstrated that availability of tumor antigens during homeostatic T cell proliferation indeed leads to effective anti-tumor autoimmunity with specificity and memory. This effect appears to be mediated by reduction in the activation threshold of low-affinity tumor-specific T cells, leading to their preferential engagement and expansion. In its simplicity, this approach is likely to have application in humans, since it relies on conventional lymphopenia-inducing cancer therapies, infusion of autologous lymphocytes and, optimally, tumor-specific vaccination.
Baccala
Roberto
R
Department of Immunology, IMM-3, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. rbaccala@scripps.edu
Gonzalez-Quintial
Rosana
R
Dummer
Wolfgang
W
Theofilopoulos
Argyrios N
AN
D000818:Animals; D001324:Autoantigens / Q000502:physiology; D015551:Autoimmunity; D006706:Homeostasis; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens