Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.

• Klíčová slova
• Hypoxia, Hypoxia-inducible factors, Immunotherapy, Personalized medicine, Tumor disease,
• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• hypoxie metabolismus   MeSH
• imunitní dozor MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory * MeSH
• únik nádoru z imunitní kontroly * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH

MHC class I presentation of short peptides enables CD8+ T cell (TCD8+) immunosurveillance of tumors and intracellular pathogens. A key feature of the class I pathway is that the immunopeptidome is highly skewed from the cellular degradome, indicating high selectivity of the access of protease-generated peptides to class I molecules. Similarly, in professional antigen-presenting cells, peptides from minute amounts of proteins introduced into the cytosol outcompete an overwhelming supply of constitutively generated peptides. Here, we propose that antigen processing is based on substrate channeling and review recent studies from the antigen processing and cell biology fields that provide a starting point for testing this hypothesis.

• MeSH
• adaptivní imunita imunologie   MeSH
• antigen prezentující buňky imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• histokompatibilita - antigeny třídy I imunologie   MeSH
• imunitní dozor imunologie   MeSH
• lidé MeSH
• peptidy imunologie   MeSH
• prezentace antigenu imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• histokompatibilita - antigeny třídy I MeSH
• peptidy MeSH

Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.

• MeSH
• cévy imunologie   MeSH
• imunitní dozor * MeSH
• integrin alfa2 genetika   imunologie   MeSH
• kůže krevní zásobení   cytologie   imunologie   MeSH
• lymfatické uzliny krevní zásobení   cytologie   imunologie   MeSH
• myši transgenní MeSH
• myši MeSH
• regulační T-lymfocyty cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• integrin alfa2 MeSH

• MeSH
• akutní lymfatická leukemie diagnóza   etiologie   metabolismus   terapie   MeSH
• biologické markery MeSH
• biopsie MeSH
• dítě MeSH
• genová přestavba MeSH
• imunitní dozor * MeSH
• klonální evoluce genetika   imunologie   MeSH
• kostní dřeň MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• prekancerózy patologie   MeSH
• translokace genetická MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

• Klíčová slova
• AllergoOncology, IgE, IgG4, allergy, atopy, biologics, desensitization, cancer, chemotherapeutic, clinical oncology, inflammation, tumor,
• MeSH
• alergie imunologie   MeSH
• imunitní dozor MeSH
• imunoglobulin E imunologie   MeSH
• imunoterapie metody   trendy   MeSH
• lidé MeSH
• nádory imunologie   terapie   MeSH
• protilátky MeSH
• Th2 buňky imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imunoglobulin E MeSH
• protilátky MeSH

γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.

• MeSH
• antigeny CD27 metabolismus   MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace MeSH
• buněčné klony cytologie   MeSH
• CX3C chemokinový receptor 1 metabolismus   MeSH
• cytotoxicita imunologická MeSH
• dárci tkání MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická variace MeSH
• hypervariabilní oblasti genetika   MeSH
• imunitní dozor * MeSH
• interleukin-15 farmakologie   MeSH
• lidé MeSH
• proliferace buněk MeSH
• receptory antigenů T-buněk gama-delta metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD27 MeSH
• biologické markery MeSH
• CX3C chemokinový receptor 1 MeSH
• CX3CR1 protein, human MeSH Prohlížeč
• hypervariabilní oblasti MeSH
• interleukin-15 MeSH
• receptory antigenů T-buněk gama-delta MeSH

Cancer can be viewed in 2 rather distinct ways, namely (i) as a cell-autonomous disease in which malignant cells have escaped control from cell-intrinsic barriers against proliferation and dissemination or (ii) as a systemic disease that involves failing immune control of aberrant cells. Since macroautophagy/autophagy generally increases the fitness of cells as well as their resistance against endogenous or iatrogenic (i.e., relating to illness due to medical intervention) stress, it has been widely proposed that inhibition of autophagy would constitute a valid strategy for sensitizing cancer cells to chemotherapy or radiotherapy. Colliding with this cell-autonomous vision, however, we found that immunosurveillance against transplantable, carcinogen-induced or genetically engineered cancers can be improved by pharmacologically inducing autophagy with caloric restriction mimetics. This positive effect depends on autophagy induction in cancer cells and is mediated by alterations in extracellular ATP metabolism, namely increased release of immunostimulatory ATP and reduced adenosine-dependent recruitment of immunosuppressive regulatory T cells into the tumor bed. The combination of autophagy inducers and chemotherapeutic agents is particularly efficient in reducing cancer growth through the stimulation of CD8+ T lymphocyte-dependent anticancer immune responses.

• Klíčová slova
• acetylation, caloric restriction mimetics, hydroxycitrate, immunosurveillance, regulatory T cells, spermidine,
• MeSH
• adenosintrifosfát metabolismus   MeSH
• autofagie * MeSH
• imunitní dozor MeSH
• lidé MeSH
• myši MeSH
• nádory imunologie   patologie   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH

Immune system must be able to protect us from foreign dangerous pathogens, but on the other side, it must be able to recognize our own tissues and organs. Activity of the immune system is affected by many positive (stimulatory) and negative (inhibitory) signals. Some of these negative receptors protect us from damage of our tissues at a place of inflammation as it blocks too intensive or longlasting immune reaction. Thereby, they have a physiological protective function against strong inflammatory reaction and possible subsequent autoimmune pathology. However, some of these mechanisms are also utilized by tumors to avoid immune recognition and attention of the immune cells. Other tumor escape mechanisms involve increased production of cytokines and factors which are responsible for immunosuppressive tumor microenvironment where effective immune response is actively blocked. This review summarizes the most frequently used strategies, which are utilized by tumors to avoid immune recognition and/ or killing by the immune cells.

• MeSH
• cytokiny biosyntéza   MeSH
• imunitní dozor * MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory imunologie   MeSH
• únik nádoru z imunitní kontroly * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

• MeSH
• cytokiny imunologie   fyziologie   MeSH
• imunitní dozor MeSH
• lidé MeSH
• myši MeSH
• poškození DNA MeSH
• stárnutí buněk imunologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• úvodníky MeSH
• Názvy látek
• cytokiny MeSH

• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• down regulace genetika   imunologie   MeSH
• genetická terapie normy   trendy   MeSH
• histokompatibilita - antigeny třídy I imunologie   metabolismus   MeSH
• imunitní dozor genetika   imunologie   MeSH
• imunoterapie normy   trendy   MeSH
• interferon gama imunologie   MeSH
• lidé MeSH
• nádorová transformace buněk genetika   imunologie   MeSH
• nádory farmakoterapie   genetika   imunologie   MeSH
• únik nádoru z imunitní kontroly genetika   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH
• Názvy látek
• histokompatibilita - antigeny třídy I MeSH
• interferon gama MeSH