Tumor Antigens
المؤلف:
Abbas, A. K., Lichtman, A. H., & Pillai, S
المصدر:
Basic Immunology : Function and disorders of immune system
الجزء والصفحة:
6th ed , page 197-199
2025-05-21
380
Malignant tumors express various types of molecules that may be recognized by the immune system as foreign antigens (Fig. 1). Protein antigens that elicit CTL responses are the most relevant for protective antitumor immunity. These tumor antigens have to be present in the cytosol of tumor cells in order to be recognized by CD8+ CTLs. The tumor antigens that elicit immune responses can be classified into several groups:
• Neoantigens encoded by randomly mutated genes. Recent sequencing of tumor genomes has revealed that common human tumors harbor a large number of mutations in diverse genes, reflecting the genetic instability of malignant cells. These mutations usually play no role in tumorigenesis and are called passenger mutations. Many of these mutations result in expression of mutated proteins, called neoantigens because they are newly expressed in the tumor cells but not in the normal cells of origin of the tumor. Because T cells only recognize peptides bound to major histocompatibility com plex (MHC) molecules, mutated tumor proteins can be recognized only if peptides carrying the mutated amino acid sequences can bind to the patients’ MHC alleles. Tumor neoantigens may not induce tolerance because they are not present in normal cells, and are the most common targets of tumor-specific adaptive immune responses. In fact, the number of these mutations in human cancers correlates with the strength of the antitumor immune responses patients mount and the effectiveness of immunotherapies that enhance those responses. In experimental tumors induced by chemical carcinogens or radiation, the tumor antigens are also mainly random mutants of normal cellular proteins.
• Products of oncogenes or mutated tumor suppressor genes. Some tumor antigens are products of mutations, called driver mutations, in genes that are involved in the process of malignant transformation. The driver mutations that encode tumor antigens may be amino acid substitutions, deletions, or new sequences generated by gene translocations, all of which can be seen as foreign.
• Aberrantly or overexpressed expressed structurally normal proteins. In several human tumors, antigens that elicit immune responses are normal (unmutated) proteins whose expression is dysregulated in the tumors, sometimes as a consequence of epigenetic changes such as demethylation of the promoters in genes encoding these proteins, and sometimes by gene amplification. These structurally normal self antigens would not be expected to elicit immune responses, but their aberrant expression may be enough to make them immunogenic. For example, self proteins that are expressed only in embryonic tissues may not induce tolerance in adults, and the same proteins expressed in tumors may be recognized as foreign by the immune system.
Fig1. Types of tumor antigens recognized by T cells. Tumor antigens that are recognized by tumor- specific CD8+ T cells may be mutated forms of various self-proteins that do not contribute to malignant behavior of the tumor; products of oncogenes or tumor suppressor genes; self-proteins whose expression is increased in tumor cells; and products of oncogenic viruses. Cancer/testis antigens are proteins that are normally expressed in the testis and are also expressed in some tumors. Tumor antigens also may be recognized by CD4+ T cells, but less is known about the role that CD4+ T cells play in tumor immunity. EBV, Epstein-Barr virus.
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