MHC class I antigens, immune surveillance, and tumor immune escape

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.

Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor

“…Our findings indicate that the blockade of b-adrenoreceptors simultaneously with the inhibition of PG synthesis (using P+E) significantly improve recurrence-free survival rates following 3LL or B16 primary tumor excision. We used these tumors given that, like most human cancers (29), both lines are poorly immunogenic, expressing no MHC-II and low levels of MHC-I (30). The B16 primary tumor was also implanted and developed orthotopically.…”

Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors

“…I t is generally thought that tumor cells can be killed by antitumor effector lymphocytes (1)(2)(3)(4)(5)(6)(7)(8). Different lymphocyte subsets are considered to be involved in this process, including CTL, ␥␦ T cells, and NK cells (1)(2)(3)(4)(5)(6)(7)(8).…”

“…Different lymphocyte subsets are considered to be involved in this process, including CTL, ␥␦ T cells, and NK cells (1)(2)(3)(4)(5)(6)(7)(8). However, it is evident that tumor cells can elude immune surveillance by several means (2)(3)(4)(5).…”

“…However, it is evident that tumor cells can elude immune surveillance by several means (2)(3)(4)(5). Indeed, CTL-mediated control can be broken out as tumor cells down-regulate HLA class I expression affecting the recognition of tumor Ag peptides (2)(3)(4)(5). This can be also accomplished by the lack, at the tumor cell surface, of costimulatory molecules and/or by the production of immunosuppressive cytokines such as TGF-␤, or by the induction of suppressor T cells (9,10).…”

Microenvironnement tumoral

“…Cependant, les tumeurs peuvent, dans certains cas, progresser et échapper, au moins en partie, à la surveillance du système immunitaire. Elles le font via la diminution du complexe majeur d'histocompatibilité de classe I (CMH I) [8] à la surface des cellules cancéreuses, ainsi que via la mise en place de cellules immunosuppressives et la sécrétion de certaines cytokines par les cellules cancéreuses, comme nous allons le décrire dans cette revue.…”