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":"The evolving landscape of immune-related adverse events that follow immune checkpoint immunotherapy in cancer patients","authors":"Alexandra-Chloé Villani","doi":"10.1111/imr.13270","DOIUrl":"https://doi.org/10.1111/imr.13270","url":null,"abstract":"&lt;p&gt;Immune checkpoint inhibitors (ICIs), including antibodies targeting anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1) have revolutionized cancer treatment.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Both PD-1 and CTLA-4 are upregulated upon T-cell activation and function to inhibit peripheral T-cell responses. These receptors maintain immune homeostasis, limiting tissue damage during infection and helping to prevent autoimmune disease. CTLA-4 suppresses T-cell activation by cell-extrinsic competition with CD28 for binding the same ligands and cell-intrinsic signaling mechanisms.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The PD-1:PD-:L1/L2 pathway also suppresses T-cell responses by inhibiting TCR/CD28 signaling, target cell lysis and cytokine production.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; PD-1 ligand is expressed across a diverse set of hematopoietic and non-hematopoietic cells, suggesting it may have more impact in peripheral tissues, whereas CTLA-4 and its ligands are primarily expressed in secondary lymphoid organs.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Collectively, ICI immunotherapy leverages this latter biology to regulate T-cell activation and tolerance, allowing the immune system to overcome cancer's evasion of immunity and reestablish its ability to attack tumor tissues.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; CTLA-4 was the first target to be approved for ICI therapy (i.e., Ipilimumab) in 2011&lt;span&gt;&lt;sup&gt;5-8&lt;/sup&gt;&lt;/span&gt; to treat advanced melanoma. Since then, eight agents targeting PD-1/PD-L1 or CTLA-4 pathways have been approved by the Food and Drug Administration (FDA) for over 20 cancer types across 80 indications.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Importantly, the utilization of ICIs in the adjuvant setting is also on the rise, resulting in further growth of the number patients receiving ICI therapy. Cancer patients treated with ICIs are now anticipated to live longer; but prolonged exposure to ICI treatment also puts them at greater risk of long-term complications associated with this line of therapy.&lt;span&gt;&lt;sup&gt;10-14&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Unfortunately, the success of ICIs is limited by the emergence of treatment-induced inflammatory toxicities, termed immune-related adverse events (irAEs). irAEs can affect any organ system in the body with a range of severity, resulting in significant morbidity for patients and considerable cost to the healthcare system. These irAEs can develop during or after treatment and often require immunosuppressive therapy or cessation of ICI treatment, thereby limiting the potential lifesaving benefits from ICI therapy.&lt;span&gt;&lt;sup&gt;1, 2, 15, 16&lt;/sup&gt;&lt;/span&gt; Depending on the treatment regimen (i.e., drug types, combination, and doses), 66%–96% of patients develop irAEs, and 7%–59% experience severe irAEs.&lt;span&gt;&lt;sup&gt;17, 18&lt;/sup&gt;&lt;/span&gt; Fulminant and fatal irAEs—the most common being myocarditis/myositis, pneumonitis, and neurologic events (e.g., Guillain–Barre syndrome and myasthenia gravis)—are experienc","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"318 1","pages":"4-10"},"PeriodicalIF":8.7,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41082134","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":"Cutaneous immune-related adverse events from immune checkpoint inhibitor therapy: Moving beyond “maculopapular rash”","authors":"Blair S. Allais,&nbsp;Christopher J. Fay,&nbsp;Daniel Y. Kim,&nbsp;Yevgeniy R. Semenov,&nbsp;Nicole R. LeBoeuf","doi":"10.1111/imr.13257","DOIUrl":"https://doi.org/10.1111/imr.13257","url":null,"abstract":"<div>\u0000 \u0000 <p>Uncoupling toxicity from therapeutic effect lies at the foundation of the current state of the field of cutaneous immune-related adverse events to immune checkpoint inhibitor therapy. This will be achieved through understanding the drivers of toxicity, tumor response, and resistance via large, well-powered population-level studies, institutional cohort data, and cellular-level data. Increasing diagnostic specificity through the application of consensus disease definitions has the power to improve clinical care and each approach to research. Cutaneous immune-related adverse events are associated with increased survival, and their treatment must invoke the maintenance of a delicate balance between immunosuppression, anti-tumor effect of immune checkpoint inhibitor therapy, and quality of life. The multidisciplinary care of cancer patients with adverse events is critical to optimizing clinical and translational research outcomes and, as such, dermatologists are vital to moving the study of cutaneous adverse events forward.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"318 1","pages":"22-36"},"PeriodicalIF":8.7,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41081619","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":"Effects of immune-related adverse events (irAEs) and their treatment on antitumor immune responses","authors":"Steven M. Blum,&nbsp;Sherin J. Rouhani,&nbsp;Ryan J. Sullivan","doi":"10.1111/imr.13262","DOIUrl":"https://doi.org/10.1111/imr.13262","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICIs) are potentially life-saving cancer therapies that can trigger immune-related adverse events (irAEs). irAEs can impact any organ and range in their presentation from mild side effects to life-threatening complications. The relationship between irAEs and antitumor immune responses is nuanced and may depend on the irAE organ, the tumor histology, and the patient. While some irAEs likely represent an immune response against antigens shared between tumor cells and healthy tissues, other irAEs may be entirely unrelated to antitumor immune responses. Clinical observations suggest that low-grade irAEs have a positive association with responses to ICIs, but the correlation between severe irAEs and clinical benefit is less clear. Currently, severe irAEs are typically treated by interrupting or permanently discontinuing ICI treatment and administering empirically selected systemic immunosuppressive agents. However, these interventions could potentially diminish the antitumor effects of ICIs. Efforts to understand the mechanistic relationship between irAEs and the tumor microenvironment have yielded meaningful insights and nominated therapeutic targets for irAE management that may preserve or even boost ICI efficacy. We explore the clinical and molecular relationship between irAEs and antitumor immunity as well as the role that irAE treatments may play in shaping antitumor immune responses.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"318 1","pages":"167-178"},"PeriodicalIF":8.7,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41082047","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":"Stocking the toolbox—Using preclinical models to understand the development and treatment of immune checkpoint inhibitor-induced immune-related adverse events","authors":"Morgan L. Cina,&nbsp;Jessica Venegas,&nbsp;Arabella Young","doi":"10.1111/imr.13250","DOIUrl":"https://doi.org/10.1111/imr.13250","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer patients treated with immune checkpoint inhibitors (ICIs) are susceptible to a broad and variable array of immune-related adverse events (irAEs). With increasing clinical use of ICIs, defining the mechanism for irAE development is more critical than ever. However, it currently remains challenging to predict when these irAEs occur and which organ may be affected, and for many of the more severe irAEs, inaccessibility to the tissue site hampers mechanistic insight. This lack of understanding of irAE development in the clinical setting emphasizes the need for greater use of preclinical models that allow for improved prediction of biomarkers for ICI-initiated irAEs or that validate treatment options that inhibit irAEs without hampering the anti-tumor immune response. Here, we discuss the utility of preclinical models, ranging from exploring databases to in vivo animal models, focusing on where they are most useful and where they could be improved.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"318 1","pages":"110-137"},"PeriodicalIF":8.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41081508","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}