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MHC class I antigens, immune surveillance, and tumor immune escape
Angel Garcia-Lora1, Ignacio Algarra, Federico Garrido
1Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain.
Abstract:
Oncogenic transformation in human and experimental animals is not necessarily followed by the appearance of a tumor mass. The immune system of the host can recognize tumor antigens by the presentation of small antigenic peptides to the receptor of cytotoxic T-lymphocytes (CTLs) and reject the nascent tumor. However, cancer cells can sometimes escape these specific T-cell immune responses in the course of somatic (genetic and phenotypic) clonal evolution. Among the tumor immune escape mechanisms described to date, the alterations in the expression of major histocompatibility complex (MHC) molecules play a crucial step in tumor development due to the role of MHC antigens in antigen presentation to T-lymphocytes and the regulation of natural killer cell (NK) cell function. In this work, we have (1) updated information on the mechanisms that allow CTLs to recognize tumor antigens after antigen processing by transformed cells, (2) described the altered MHC class I phenotypes that are commonly found in human tumors, (3) summarized the molecular mechanisms responsible for MHC class I alteration in human tumors, (4) provided evidence that these altered human leukocyte antigens (HLA) class I phenotypes are detectable as result of a T-cell immunoselection of HLA class I-deficient variants by an immunecompetent host, and (5) presented data indicating the MHC class I phenotype and the immunogenicity of experimental metastatic tumors change drastically when tumors develop in immunodeficient mice.
Insights
Cancer cells can evade immune detection by altering their Major Histocompatibility Complex (MHC) class I expression. This study details how these alterations facilitate tumor immune escape and impact cancer progression.
Area of Science:
- Immunology
- Cancer Biology
- Genetics
Background:
- The immune system can reject nascent tumors by recognizing tumor antigens via cytotoxic T-lymphocytes (CTLs).
- Cancer cells can escape T-cell surveillance through somatic clonal evolution.
- Alterations in Major Histocompatibility Complex (MHC) molecule expression are key tumor immune escape mechanisms.
Purpose of the Study:
- To update knowledge on how CTLs recognize tumor antigens.
- To describe altered MHC class I phenotypes in human tumors.
- To investigate the role of MHC alterations in tumor immune escape and development.
Main Methods:
- Review of mechanisms for CTL recognition of tumor antigens.
- Analysis of MHC class I expression alterations in human tumors.
- Examination of experimental metastatic tumors in immunodeficient mice.
Main Results:
- CTLs recognize tumor antigens processed by transformed cells.
- Altered MHC class I (human leukocyte antigen [HLA] class I) phenotypes are common in human tumors.
- These HLA class I alterations result from T-cell immunoselection of deficient variants.
- MHC class I phenotype and immunogenicity change in tumors grown in immunodeficient hosts.
Conclusions:
- Altered MHC class I expression is a critical mechanism for tumor immune escape.
- T-cell-mediated immune pressure drives the selection of MHC class I-deficient tumor variants.
- Understanding these mechanisms is crucial for developing effective cancer immunotherapies.