Coupling and Uncoupling of Tumor Immunity and Autoimmunity
نویسندگان
چکیده
Self-antigens, in the form of differentiation antigens, are commonly recognized by the immune system on melanoma and other cancers. We have shown previously that active immunization of mice against the melanocyte differentiation antigen, a tyrosinase-related protein (TRP) gp75(TRP-1) (the brown locus protein) expressed by melanomas, could induce tumor immunity and autoimmunity manifested as depigmentation. In this system, tumor immunity and autoimmunity were mediated by autoantibodies. Here, we characterize immunity against another tyrosinase family glycoprotein TRP-2 (the slaty locus protein), using the same mouse model and method of immunization. As observed previously for gp75(TRP-1), immunity was induced by DNA immunization against a xenogeneic form of TRP-2, but not against the syngeneic gene, and depended on CD4(+) cells. Immunization against TRP-2 induced autoantibodies and autoreactive cytotoxic T cells. In contrast to immunization against gp75(TRP-1), both tumor immunity and autoimmunity required CD8(+) T cells, but not antibodies. Only autoimmunity required perforin, whereas tumor immunity proceeded in the absence of perforin. Thus, immunity induced against two closely related autoantigens that are highly conserved throughout vertebrate evolution involved qualitatively different mechanisms, i.e., antibody versus CD8(+) T cell. However, both pathways led to tumor immunity and identical phenotypic manifestations of autoimmunity.
منابع مشابه
Role of miR-146a in Immune System and Autoimmunity
MicroRNAs (miRNAs) are small preserved non-coding RNA molecules that regulate gene expression post-transcriptionally by targeting the 3' UTR of mRNAs for translational repression or degradation. The rising evidence has established the significant role of miRNAs within the regulation of immune system and the prevention of autoimmunity. MiR-146a has obtained an importance as a modulator of differ...
متن کاملDendritic Cell Immunotherapy, the Next Step in Cancer Treatment
Cancer immunotherapy has gained a lot of interest over the past few years due to the success of immune checkpoint inhibitors in treating cancer (1, 2). Immune checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), have been shown to increase survival of patients with advanced cancers (1, 2). These in...
متن کاملDendritic Cell Immunotherapy, the Next Step in Cancer Treatment
Cancer immunotherapy has gained a lot of interest over the past few years due to the success of immune checkpoint inhibitors in treating cancer (1, 2). Immune checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), have been shown to increase survival of patients with advanced cancers (1, 2). These in...
متن کاملTwo Dimensional Mathematical Model of Tumor Angiogenesis: Coupling of Avascular Growth and Vascularization
Introduction As a tumor grows, the demand for oxygen and nutrients increases and it grows further if acquires the ability to induce angiogenesis. In this study, we aimed to present a two-dimensional continuous mathematical model for avascular tumor growth, coupled with a discrete model of angiogenesis. Materials and Methods In the avascular growth model, tumor is considered as a single mass, wh...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of Experimental Medicine
دوره 190 شماره
صفحات -
تاریخ انتشار 1999