Immunological Reviews最新文献

{"title":"Type I interferon and cancer","authors":"Peter Holicek,&nbsp;Emma Guilbaud,&nbsp;Vanessa Klapp,&nbsp;Iva Truxova,&nbsp;Radek Spisek,&nbsp;Lorenzo Galluzzi,&nbsp;Jitka Fucikova","doi":"10.1111/imr.13272","DOIUrl":"10.1111/imr.13272","url":null,"abstract":"<p>Type I interferon (IFN) is a class of proinflammatory cytokines with a dual role on malignant transformation, tumor progression, and response to therapy. On the one hand, robust, acute, and resolving type I IFN responses have been shown to mediate prominent anticancer effects, reflecting not only their direct cytostatic/cytotoxic activity on (at least some) malignant cells, but also their pronounced immunostimulatory functions. In line with this notion, type I IFN signaling has been implicated in the antineoplastic effects of various immunogenic therapeutics, including (but not limited to) immunogenic cell death (ICD)-inducing agents and immune checkpoint inhibitors (ICIs). On the other hand, weak, indolent, and non-resolving type I IFN responses have been demonstrated to support tumor progression and resistance to therapy, reflecting the ability of suboptimal type I IFN signaling to mediate cytoprotective activity, promote stemness, favor tolerance to chromosomal instability, and facilitate the establishment of an immunologically exhausted tumor microenvironment. Here, we review fundamental aspects of type I IFN signaling and their context-dependent impact on malignant transformation, tumor progression, and response to therapy.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"321 1","pages":"115-127"},"PeriodicalIF":8.7,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-mediated phagocytosis in cancer immunotherapy","authors":"Carly M. Van Wagoner,&nbsp;Fátima Rivera-Escalera,&nbsp;Nydia C. Jaimes-Delgadillo,&nbsp;Charles C. Chu,&nbsp;Clive S. Zent,&nbsp;Michael R. Elliott","doi":"10.1111/imr.13265","DOIUrl":"10.1111/imr.13265","url":null,"abstract":"&lt;p&gt;Targeted therapy, a goal first popularized by Paul Erlich in the 19th century,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; has the potential to increase the efficacy and decrease toxicity of treatment for malignancies. Capability to manufacture monoclonal antibodies (mAbs) in the 1970s followed by genetic engineering to develop chimeric, humanized and then fully human mAb constructs to overcome the development of neutralizing antibodies by patients resulted in the ability to make targeted mAb.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; These mAb can bind target cells to activate immune cytotoxicity, induce apoptosis, block ligation of cell surface receptors or sequestrate their ligands. The prototypic mAbs rituximab (chimeric mouse/human IgG1) and alemtuzumab (humanized rat/human IgG1) that activated innate immune cytotoxicity were clinically effective and tolerable. Rituximab was approved by the FDA for treatment of B-cell non-Hodgkin lymphomas in 1997 and alemtuzumab for treatment of chronic lymphocytic leukemia in 2001. Rituximab, alemtuzumab and next generation mAbs have significantly improved treatment outcomes for several human malignancies by mechanisms that include mAb-induced antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). To date, the best studied mAb for which ADCP is a major mechanism of action has been in B-cell malignancies, which will be the clinical focus of this review.&lt;/p&gt;&lt;p&gt;The two main forms of cellular phagocytosis are efferocytosis (the engulfment of dead or dying cells) and ADCP.&lt;span&gt;&lt;sup&gt;4-8&lt;/sup&gt;&lt;/span&gt; Despite decades of research into the mechanisms of cellular phagocytosis, this innate immune effector mechanism is still underutilized as means for the targeted killing of malignant cells. This is due in part to our lack of information on how ADCP is carried out in vivo and a poor understanding of the factors that control the efficacy of mAbs in vivo. In recent years, important studies in mice have revealed key new insights into how ADCP-inducing mAbs traffic in the body and how phagocytes recognize and clear mAb-opsonized target cells. At the same time, advances in therapeutic antibody design, including glyco-engineering and the development of hexameric and mAbs, have opened new avenues to leverage the power of ADCP for better clearance of malignant cells in a wide range of cancers. Here, we will first review our current understanding of the cellular and molecular mechanisms of ADCP and the current state of ADCP-inducing mAbs used in human cancer. Then we will discuss key factors that control ADCP in the context of mAb cancer immunotherapy and to provide perspective on some of the most important and outstanding questions in this field.&lt;/p&gt;&lt;p&gt;Therapeutic mAb-mediated cytotoxicity can be induced by direct cytototoxic effects, receptor blockade, and activation of innate immune cytotoxicity by ADCP, ADCC, and CDC.&lt;span&gt;&lt;sup&gt;47, 48&lt;/sup&gt;&lt;/span&gt; The mechanisms of ","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"128-141"},"PeriodicalIF":8.7,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAM receptors in phagocytosis: Beyond the mere internalization of particles","authors":"Tal Burstyn-Cohen,&nbsp;Roberta Fresia","doi":"10.1111/imr.13267","DOIUrl":"10.1111/imr.13267","url":null,"abstract":"TYRO3, AXL, and MERTK constitute the TAM family of receptor tyrosine kinases, activated by their ligands GAS6 and PROS1. TAMs are necessary for adult homeostasis in the immune, nervous, reproductive, skeletal, and vascular systems. Among additional cellular functions employed by TAMs, phagocytosis is central for tissue health. TAM receptors are dominant in providing phagocytes with the molecular machinery necessary to engulf diverse targets, including apoptotic cells, myelin debris, and portions of live cells in a phosphatidylserine‐dependent manner. Simultaneously, TAMs drive the release of anti‐inflammatory and tissue repair molecules. Disruption of the TAM‐driven phagocytic pathway has detrimental consequences, resulting in autoimmunity, male infertility, blindness, and disrupted vascular integrity, and which is thought to contribute to neurodegenerative diseases. Although structurally and functionally redundant, the TAM receptors and ligands underlie complex signaling cascades, of which several key aspects are yet to be elucidated. We discuss similarities and differences between TAMs and other phagocytic pathways, highlight future directions and how TAMs can be harnessed therapeutically to modulate phagocytosis.","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"7-26"},"PeriodicalIF":8.7,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10402511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenic cell death (ICD) enhancers—Drugs that enhance the perception of ICD by dendritic cells","authors":"Peng Liu,&nbsp;Liwei Zhao,&nbsp;Laurence Zitvogel,&nbsp;Oliver Kepp,&nbsp;Guido Kroemer","doi":"10.1111/imr.13269","DOIUrl":"10.1111/imr.13269","url":null,"abstract":"<p>The search for immunostimulatory drugs applicable to cancer immunotherapy may profit from target-agnostic methods in which agents are screened for their functional impact on immune cells cultured in vitro without any preconceived idea on their mode of action. We have built a synthetic mini-immune system in which stressed and dying cancer cells (derived from standardized cell lines) are confronted with dendritic cells (DCs, derived from immortalized precursors) and CD8⁺ T-cell hybridoma cells expressing a defined T-cell receptor. Using this system, we can identify three types of immunostimulatory drugs: (i) pharmacological agents that stimulate immunogenic cell death (ICD) of malignant cells; (ii) drugs that act on DCs to enhance their response to ICD; and (iii) drugs that act on T cells to increase their effector function. Here, we focus on strategies to develop drugs that enhance the perception of ICD by DCs and to which we refer as “ICD enhancers.” We discuss examples of ICD enhancers, including ligands of pattern recognition receptors (exemplified by TLR3 ligands that correct the deficient function of DCs lacking FPR1) and immunometabolic modifiers (exemplified by hexokinase-2 inhibitors), as well as methods for target deconvolution applicable to the mechanistic characterization of ICD enhancers.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"321 1","pages":"7-19"},"PeriodicalIF":8.7,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10027083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using immunogenic cell death to improve anticancer efficacy of immune checkpoint inhibitors: From basic science to clinical application","authors":"François Ghiringhelli,&nbsp;Cédric Rébé","doi":"10.1111/imr.13263","DOIUrl":"10.1111/imr.13263","url":null,"abstract":"<p>Even though the discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, a high proportion of patients do not respond. Moreover, some types of cancers are refractory to these treatments. Thus, the need to find predictive biomarkers of efficacy and to evaluate the association with other treatments, such as chemotherapy or radiotherapy, appears to be essential. Because ICIs reactivate or maintain an active status of T cells, one possibility is to combine these treatments with therapies that engage an immune response against tumor cells. Thus, by inducing immunogenic cell death (ICD) of cancer cells, some conventional anticancer treatments induce such immune response and may have an interest to be combined with ICIs. In this review, we explore preclinical studies and clinical trials that evaluate the combination of ICIs with ICD inducers. More than inducing ICD, some of these treatments appear to modulate the tumor microenvironment and more particularly to inhibit immunosuppression, thus improving treatment efficacy.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"321 1","pages":"335-349"},"PeriodicalIF":8.7,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the diversity and dynamics of in vivo efferocytosis: Insights from the fly embryo","authors":"Rosalind Heron,&nbsp;Clelia Amato,&nbsp;Will Wood,&nbsp;Andrew J. Davidson","doi":"10.1111/imr.13266","DOIUrl":"10.1111/imr.13266","url":null,"abstract":"<p>The clearance of dead and dying cells, termed efferocytosis, is a rapid and efficient process and one that is critical for organismal health. The extraordinary speed and efficiency with which dead cells are detected and engulfed by immune cells within tissues presents a challenge to researchers who wish to unravel this fascinating process, since these fleeting moments of uptake are almost impossible to catch in vivo. In recent years, the fruit fly (<i>Drosophila melanogaster)</i> embryo has emerged as a powerful model to circumvent this problem. With its abundance of dying cells, specialist phagocytes and relative ease of live imaging, the humble fly embryo provides a unique opportunity to catch and study the moment of cell engulfment in real-time within a living animal. In this review, we explore the recent advances that have come from studies in the fly, and how live imaging and genetics have revealed a previously unappreciated level of diversity in the efferocytic program. A variety of efferocytic strategies across the phagocytic cell population ensure efficient and rapid clearance of corpses wherever death is encountered within the varied and complex setting of a multicellular living organism.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"27-44"},"PeriodicalIF":8.7,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10368292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clearance phagocytosis by the retinal pigment epithelial during photoreceptor outer segment renewal: Molecular mechanisms and relation to retinal inflammation","authors":"Stephanie A. Lieffrig,&nbsp;Gavin Gyimesi,&nbsp;Yingyu Mao,&nbsp;Silvia C. Finnemann","doi":"10.1111/imr.13264","DOIUrl":"10.1111/imr.13264","url":null,"abstract":"<div>\u0000 \u0000 <p>Mammalian photoreceptor outer segment renewal is a highly coordinated process that hinges on timed cell signaling between photoreceptor neurons and the adjacent retinal pigment epithelial (RPE). It is a strictly rhythmic, synchronized process that underlies in part circadian regulation. We highlight findings from recently developed methods that quantify distinct phases of outer segment renewal in retinal tissue. At light onset, outer segments expose the conserved “eat-me” signal phosphatidylserine exclusively at their distal, most aged tip. A coordinated two-receptor efferocytosis process follows, in which ligands bridge outer segment phosphatidylserine with the RPE receptors αvβ5 integrin, inducing cytosolic signaling toward Rac1 and focal adhesion kinase/MERTK, and with MERTK directly, additionally inhibiting RhoA/ROCK and thus enabling F-actin dynamics favoring outer segment fragment engulfment. Photoreceptors and RPE persist for life with each RPE cell in the eye servicing dozens of overlying photoreceptors. Thus, RPE cells phagocytose more often and process more material than any other cell type. Mutant mice with impaired outer segment renewal largely retain functional photoreceptors and retinal integrity. However, when anti-inflammatory signaling in the RPE via MERTK or the related TYRO3 is lacking, catastrophic inflammation leads to immune cell infiltration that swiftly destroys the retina causing blindness.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"81-99"},"PeriodicalIF":8.7,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis","authors":"Christopher D. Gregory","doi":"10.1111/imr.13259","DOIUrl":"10.1111/imr.13259","url":null,"abstract":"<p>Cancers are genetically driven, rogue tissues which generate dysfunctional, obdurate organs by hijacking normal, homeostatic programs. Apoptosis is an evolutionarily conserved regulated cell death program and a profoundly important homeostatic mechanism that is common (alongside tumor cell proliferation) in actively growing cancers, as well as in tumors responding to cytotoxic anti-cancer therapies. Although well known for its cell-autonomous tumor-suppressive qualities, apoptosis harbors pro-oncogenic properties which are deployed through non-cell-autonomous mechanisms and which generally remain poorly defined. Here, the roles of apoptosis in tumor biology are reviewed, with particular focus on the secreted and fragmentation products of apoptotic tumor cells and their effects on tumor-associated macrophages, key supportive cells in the aberrant homeostasis of the tumor microenvironment. Historical aspects of cell loss in tumor growth kinetics are considered and the impact (and potential impact) on tumor growth of apoptotic-cell clearance (efferocytosis) as well as released soluble and extracellular vesicle-associated factors are discussed from the perspectives of inflammation, tissue repair, and regeneration programs. An “apoptosis-centric” view is proposed in which dying tumor cells provide an important platform for intricate intercellular communication networks in growing cancers. The perspective has implications for future research and for improving cancer diagnosis and therapy.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"100-127"},"PeriodicalIF":8.7,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The resolution of phagosomes","authors":"Sivakami Mylvaganam,&nbsp;Spencer A. Freeman","doi":"10.1111/imr.13260","DOIUrl":"10.1111/imr.13260","url":null,"abstract":"<div>\u0000 \u0000 <p>Phagocytosis is a fundamental immunobiological process responsible for the removal of harmful particulates. While the number of phagocytic events achieved by a single phagocyte can be remarkable, exceeding hundreds per day, the same phagocytic cells are relatively long-lived. It should therefore be obvious that phagocytic meals must be resolved in order to maintain the responsiveness of the phagocyte and to avoid storage defects. In this article, we discuss the mechanisms involved in the resolution process, including solute transport pathways and membrane traffic. We describe how products liberated in phagolysosomes support phagocyte metabolism and the immune response. We also speculate on mechanisms involved in the redistribution of phagosomal metabolites back to circulation. Finally, we highlight the pathologies owed to impaired phagosome resolution, which range from storage disorders to neurodegenerative diseases.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"319 1","pages":"45-64"},"PeriodicalIF":8.7,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbes mediated immunogenic cell death in cancer immunotherapy","authors":"Jumin Huang,&nbsp;Fugang Duan,&nbsp;Chun Xie,&nbsp;Jiahui Xu,&nbsp;Yizhong Zhang,&nbsp;Yuwei Wang,&nbsp;Yu-Ping Tang,&nbsp;Elaine Lai-Han Leung","doi":"10.1111/imr.13261","DOIUrl":"10.1111/imr.13261","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage-associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD-based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD-relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe-mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"321 1","pages":"128-142"},"PeriodicalIF":8.7,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}