MHC class I Dotaz Zobrazit nápovědu
MHC class I downregulation is a general mechanism by which tumor cells can escape from T-cell-mediated immunity. This downregulation also represents a serious obstacle to the development of effective antitumor immunotherapy or vaccination. Therefore, successful immunotherapeutic and vaccination protocols should be optimized against tumors with distinct cell surface expression of the MHC class I molecules. Mechanisms leading to protective immunity may vary in different models with respect to the particular tumors (e.g., in their levels of residual expression of the MHC class I molecules on tumor cells or inducibility of MHC class I expression). Notably, both CD8(+) cell-mediated immunity and MHC class I-unrestricted mechanisms can take place against MHC class I-deficient tumors. Since MHC class I downregulation is frequently reversible by cytokines and also by the activation of epigenetically silenced genes, an attractive strategy is to elicit specific cell-mediated immunity combined with restoration of MHC class I expression on tumor cells.
- MeSH
- histokompatibilita - antigeny třídy I biosyntéza imunologie MeSH
- imunoterapie metody MeSH
- lidé MeSH
- nádory imunologie terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition. The potential for the use of a PD-1/PD-L1 blockade in the treatment of tumors with aberrant MHC class I expression is discussed, and some strategies of combination therapy are suggested.
- MeSH
- antigeny CD274 antagonisté a inhibitory imunologie MeSH
- antigeny CD279 antagonisté a inhibitory imunologie MeSH
- down regulace * MeSH
- geny MHC třídy I MeSH
- histokompatibilita - antigeny třídy I genetika MeSH
- imunoterapie metody MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- nádory genetika imunologie terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The human molecular genetics series
1st ed. 17, 438 s. : il.
- MeSH
- genetika člověka MeSH
- geny MHC třídy I MeSH
- geny MHC třídy II MeSH
- HLA-A antigeny MeSH
- imunita MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
- biologie
Proteins encoded by antigen-processing genes (APGs) prepare antigens for presentation by the major histocompatibility complex class I (MHC I) molecules. Coevolution between APGs and MHC I genes has been proposed as the ancestral gnathostome condition. The hypothesis predicts a single highly expressed MHC I gene and tight linkage between APGs and MHC I. In addition, APGs should evolve under positive selection, a consequence of the adaptive evolution in MHC I. The presence of multiple highly expressed MHC I genes in some teleosts, birds, and urodeles appears incompatible with the coevolution hypothesis. Here, we use urodele amphibians to test two key expectations derived from the coevolution hypothesis: 1) the linkage between APGs and MHC I was studied in Lissotriton newts and 2) the evidence for adaptive evolution in APGs was assessed using 42 urodele species comprising 21 genera from seven families. We demonstrated that five APGs (PSMB8, PSMB9, TAP1, TAP2, and TAPBP) are tightly linked (<0.5 cM) to MHC I. Although all APGs showed some codons under episodic positive selection, we did not find a pervasive signal of positive selection expected under the coevolution hypothesis. Gene duplications, putative gene losses, and divergent allelic lineages detected in some APGs demonstrate considerable evolutionary dynamics of APGs in salamanders. Overall, our results indicate that if coevolution between APGs and MHC I occurred in urodeles, it would be more complex than envisaged in the original formulation of the hypothesis.
- MeSH
- duplikace genu MeSH
- genetická vazba MeSH
- geny MHC třídy I * MeSH
- molekulární evoluce * MeSH
- prezentace antigenu genetika MeSH
- proteiny obojživelníků chemie klasifikace genetika MeSH
- Urodela genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 30 cm
In this grant project it will be investigated whether there is a lack of immunological cross-reactivity between MHC class I positive and MHC class I negative tumours. It will be determined whether cytotoxic T lymphocytes recognise as targets tumour cellsexpressing supra-treshold levels of the MHC class I molecules. It will be investigated whether T helper cells play a role in the immune response against both MHC class I positive and negative tumours.
V rámci grantového projektu bude potvrzeno nebo vyvráceno, že není imunologická zkřížená reaktivita mezi MHC I positivními MHC I negativníni nádory stejné etiologie. Bude zjištěno, jaká je nadprahová úroveň exprese MHC I, aby byla nádorová buňka rozpoznána specifickými cytotoxickými lymfocyty. Bude studováno, jakou roli hrají pomocné lymfocyty v imunitní odpovědí proti MHC I positivním a negativním nádorům.
- MeSH
- geny MHC třídy I účinky léků MeSH
- imunoterapie MeSH
- infekce onkogenními viry MeSH
- lidský papilomavirus 16 MeSH
- nádory terapie MeSH
- Papillomaviridae MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- onkologie
- hematologie a transfuzní lékařství
- alergologie a imunologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape from T-cell mediated immune responses. In this study we have investigated the immunologic crossreactivity between murine tumour cell lines expressing human papilloma virus (HPV) 16-derived E6/E7 oncoproteins with distinct surface expression of MHC class I molecules. The aims of this study were to demonstrate whether immune responses capable of coping with MHC class I-positive tumours can also be effective against their MHC class I-deficient derivatives and whether it is possible to induce immunity against MHC class I-deficient tumours by cellular vaccines based on MHC class I-deficient tumour cell lines. Our data showed that immunization with MHC class I-deficient but not with MHC class I positive tumour cells inhibited the growth of MHC class I-deficient tumours. In vivo depletion studies revealed that the mechanisms underlying effective immune responses against MHC class I-negative tumours in animals immunized with MHC class I-deficient tumour cells involved natural killer cells. The presented findings are of particular clinical relevance in the sense of construction of vaccines directed against a broad spectrum of HPV-associated tumours.
- MeSH
- financování organizované MeSH
- histokompatibilita - antigeny třídy I analýza imunologie MeSH
- imunizace MeSH
- lidský papilomavirus 16 imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory imunologie terapie virologie MeSH
- proliferace buněk MeSH
- protinádorové vakcíny terapeutické užití MeSH
- zkřížené reakce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
