"Tumor-antigenicity" or the 'antigenicity' of a tumor is the extent to which tumor cells display human leukocyte antigen (HLA)-restricted antigens that can be selectively or explicitly recognized by T cells.
Many tumors produce antigens. These tumor-specific antigens can be released into the bloodstream or remain on cell surfaces. Any molecule recognized by the immune system is an antigen.
Immunologists hypothesized that mutational processes associated with tumorigenesis result in tumors. The formation of tumors induces the presentation of mutated peptide antigens called "neo-antigens" or "neo-epitopes," regions of antigens generated by modification of the original antigen. T cells recognize the presented neo-epitopes, which is often associated with a pathologic process. The notion is that mutation may induce neo-epitopes in two ways.
(i) Mutations may fall within an epitope generally presented on the cell surface via HLA molecules. These mutations thereby
alter the epitope and permit recognition by specific T cells.
(ii) Mutations may change the processing of a given peptide in antigen presentation pathways. For example, the proteolytic
cleavage or HLA binding may result in a newly presented peptide.
How do we know this?
Tumor-expressed, HLA-restricted neo-antigens originate primarily from sporadic cases. Researchers noticed that patient-derived T cell lines reactive to autologous tumor cells recognize a mutated neo-epitope. In general, point mutations induce single amino-acid changes present in neo-epitopes. Also, translocation junction points can result in neo-epitopes as well.
Reference
Buonaguro L, Petrizzo A, Tornesello ML, Buonaguro FM. Translating tumor antigens into cancer vaccines. Clin Vaccine Immunol. 2011 Jan;18(1):23-34. [PMC]
Peter A. Savage; Tumor antigenicity revealed. Trends in Immunology, February 2014, Vol. 35, No. 2 47-48. [PMC]
Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L. Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother. 2014;10(11):3332-46. [PMC]
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