The skin is the first line of defense to prevent entry of pathogenic bacteria from the environment and their dissemination to internal organs.This crucial function is accomplished mostly by keratinocytes,which serve a...The skin is the first line of defense to prevent entry of pathogenic bacteria from the environment and their dissemination to internal organs.This crucial function is accomplished mostly by keratinocytes,which serve as a physical barrier and produce antimicrobial peptides.展开更多
Dendritic cells(DCs)exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses.Due to their ability to cross-present tumor cell-associated antigens to naï...Dendritic cells(DCs)exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses.Due to their ability to cross-present tumor cell-associated antigens to naïve T cells,DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination.Within an immunosuppressive tumor microenvironment,DC antitumor functions can,however,be severely impaired.In this review,we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions,taking advantage of recent studies showing the phenotype acquisition,transcriptional state and functional programs revealed by scRNA-seq analysis.The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.展开更多
Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for thedevelopment of immune tolerance. Immature DCs reside in peripheral tissues and spe...Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for thedevelopment of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas matureDCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs isstrictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (dangerassociated molecular patterns), complement proteins, lipids, and chemokines. These signals function both individually and inconcert, generating a complex regulatory network. This network is regulated at multiple levels through different strategies, such assynergistic interactions, proteolytic processing, and the actions of atypical chemokine receptors. Understanding this complexscenario will help to clarify the role of DCs in different pathological conditions, such as autoimmune diseases and cancers and willuncover new molecular targets for therapeutic interventions.展开更多
基金AIRC-IG 2023(ID 29244),PRIN-2022(20228KZKE3)European Union-Next Generation EU in the context of The National Recovery and Resilience Plan,Investment Partenariato Esteso PE8“Conseguenze e sfide dell’invecchiamento”,Project Age-It(Aging Well in an Aging Society).
文摘The skin is the first line of defense to prevent entry of pathogenic bacteria from the environment and their dissemination to internal organs.This crucial function is accomplished mostly by keratinocytes,which serve as a physical barrier and produce antimicrobial peptides.
基金the Italian Association for Cancer Research(AIRC IG-2017/20776 to SS and IG-2021/25680 to AS)Ministero dell'lstruzione,dell'Universita e della Ricerca(MIUR,PRIN Prot.2017/7J4E75 to SS,2017/8ALPCM_005 to DB)ML was the recipient of a fellowship from AIRC(code 25307).
文摘Dendritic cells(DCs)exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses.Due to their ability to cross-present tumor cell-associated antigens to naïve T cells,DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination.Within an immunosuppressive tumor microenvironment,DC antitumor functions can,however,be severely impaired.In this review,we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions,taking advantage of recent studies showing the phenotype acquisition,transcriptional state and functional programs revealed by scRNA-seq analysis.The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.
基金This work was supported by AIRC(Associazione Italiana Ricerca sul Cancro),IAP(Interuniversity Attraction Poles)7-40 program,COST action BM1404 Mye-EUNITER,CARIPLO,and Ministero Salute.
文摘Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for thedevelopment of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas matureDCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs isstrictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (dangerassociated molecular patterns), complement proteins, lipids, and chemokines. These signals function both individually and inconcert, generating a complex regulatory network. This network is regulated at multiple levels through different strategies, such assynergistic interactions, proteolytic processing, and the actions of atypical chemokine receptors. Understanding this complexscenario will help to clarify the role of DCs in different pathological conditions, such as autoimmune diseases and cancers and willuncover new molecular targets for therapeutic interventions.
