Immunotherapy advances最新文献_第7页

Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy. 肥胖和脂肪组织对t细胞反应和癌症免疫检查点阻断治疗的影响。

Immunotherapy advances Pub Date : 2022-06-24 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac015

Gabriel Pasquarelli-do-Nascimento, Sabrina Azevedo Machado, Juliana Maria Andrade de Carvalho, Kelly Grace Magalhães

{"title":"Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy.","authors":"Gabriel Pasquarelli-do-Nascimento, Sabrina Azevedo Machado, Juliana Maria Andrade de Carvalho, Kelly Grace Magalhães","doi":"10.1093/immadv/ltac015","DOIUrl":"https://doi.org/10.1093/immadv/ltac015","url":null,"abstract":"Many different types of cancer are now well known to have increased occurrence or severity in individuals with obesity. The influence of obesity on cancer and the immune cells in the tumor microenvironment has been thought to be a pleiotropic effect. As key endocrine and immune organs, the highly plastic adipose tissues play crucial roles in obesity pathophysiology, as they show alterations according to environmental cues. Adipose tissues of lean subjects present mostly anti-inflammatory cells that are crucial in tissue remodeling, favoring uncoupling protein 1 expression and non-shivering thermogenesis. Oppositely, obese adipose tissues display massive proinflammatory immune cell infiltration, dying adipocytes, and enhanced crown-like structure formation. In this review, we discuss how obesity can lead to derangements and dysfunctions in antitumor CD8+ T lymphocytes dysfunction. Moreover, we explain how obesity can affect the efficiency of cancer immunotherapy, depicting the mechanisms involved in this process. Cancer immunotherapy management includes monoclonal antibodies targeting the immune checkpoint blockade. Exhausted CD8+ T lymphocytes show elevated programmed cell death-1 (PD-1) expression and highly glycolytic tumors tend to show a good response to anti-PD-1/PD-L1 immunotherapy. Although obesity is a risk factor for the development of several neoplasms and is linked with increased tumor growth and aggressiveness, obesity is also related to improved response to cancer immunotherapy, a phenomenon called the obesity paradox. However, patients affected by obesity present higher incidences of adverse events related to this therapy. These limitations highlight the necessity of a deeper investigation of factors that influence the obesity paradox to improve the application of these therapies.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":"ltac015"},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33443195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Corrigendum to: 100 years post-insulin: immunotherapy as the next frontier in type 1 diabetes. 胰岛素后100年:免疫疗法作为1型糖尿病的下一个前沿。

Immunotherapy advances Pub Date : 2022-06-22 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac013

引用次数: 0

Adrenergic signaling regulation of macrophage function: do we understand it yet? 巨噬细胞功能的肾上腺素能信号调节：我们还了解吗？

Immunotherapy advances Pub Date : 2022-06-01 DOI: 10.1093/immadv/ltac010

B. M. Freire, F. M. de Melo, A. Basso

{"title":"Adrenergic signaling regulation of macrophage function: do we understand it yet?","authors":"B. M. Freire, F. M. de Melo, A. Basso","doi":"10.1093/immadv/ltac010","DOIUrl":"https://doi.org/10.1093/immadv/ltac010","url":null,"abstract":"Abstract Macrophages are immune cells that are widespread throughout the body and critical for maintaining tissue homeostasis. Their remarkable plasticity allows them to acquire different phenotypes, becoming able either to fight infection (M1-like, classically activated macrophages) or to promote tissue remodeling and repair (M2-like, alternatively activated macrophages). These phenotypes are induced by different cues present in the microenvironment. Among the factors that might regulate macrophage activation are mediators produced by different branches of the nervous system. The regulation exerted by the sympathetic nervous system (SNS) on macrophages (and the immune system in general) is becoming a subject of increasing interest, indeed a great number of articles have been published lately. Catecholamines (noradrenaline and adrenaline) activate α and β adrenergic receptors expressed by macrophages and shape the effector functions of these cells in contexts as diverse as the small intestine, the lung, or the adipose tissue. Activation of different subsets of receptors seems to produce antagonistic effects, with α adrenergic receptors generally associated with pro-inflammatory functions and β adrenergic receptors (particularly β2) related to the resolution of inflammation and tissue remodeling. However, exceptions to this paradigm have been reported, and the factors contributing to these apparently contradictory observations are still far from being completely understood. Additionally, macrophages per se seem to be sources of catecholamines, which is also a subject of some debate. In this review, we discuss how activation of adrenergic receptors modulates macrophage effector functions and its implications for inflammatory responses and tissue homeostasis.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44712837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Current and future perspectives of chimeric antigen receptors against glioblastoma 胶质母细胞瘤嵌合抗原受体的研究现状与展望

Immunotherapy advances Pub Date : 2022-06-01 DOI: 10.1093/immadv/ltac014

Josephine Zhang, Jesús A. Siller-Farfán

{"title":"Current and future perspectives of chimeric antigen receptors against glioblastoma","authors":"Josephine Zhang, Jesús A. Siller-Farfán","doi":"10.1093/immadv/ltac014","DOIUrl":"https://doi.org/10.1093/immadv/ltac014","url":null,"abstract":"Abstract Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49654647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy. 靶异构体是嵌合抗原受体细胞治疗中被忽视的挑战和机遇。

Immunotherapy advances Pub Date : 2022-04-20 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac009

Mike Bogetofte Barnkob, Kristoffer Vitting-Seerup, Lars Rønn Olsen

引用次数: 8

Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors. 平衡好与坏:在接受免疫检查点抑制剂治疗的癌症患者中控制免疫相关不良事件与抗肿瘤反应

Immunotherapy advances Pub Date : 2022-04-08 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac008

Guilherme Ferreira de Britto Evangelista, Amanda Braga Figueiredo, Milton José de Barros E Silva, Kenneth J Gollob

{"title":"Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors.","authors":"Guilherme Ferreira de Britto Evangelista, Amanda Braga Figueiredo, Milton José de Barros E Silva, Kenneth J Gollob","doi":"10.1093/immadv/ltac008","DOIUrl":"https://doi.org/10.1093/immadv/ltac008","url":null,"abstract":"Immune checkpoint inhibitors (ICI) have provided new hope for cancer patients, and in particular for patients with tumors that are immunologically active and classified as hot tumors. These tumors express antigenic and tumor microenvironment (TME) characteristics that make them potential candidates for therapy with checkpoint inhibitors that aim to reactivate the immune response such as anti-PD-1 and anti-CTLA-4. Examples of potentially responsive cancers are, melanoma, non-small cell lung cancer and several other metastatic or unresectable tumors with genetic instability: DNA mismatch repair deficiency (dMMR), microsatellite instability-high (MSI-H), or with a high tumor mutational burden (TMB). Immunotherapy using checkpoint inhibitors is typically associated with adverse events (AEs) that are milder than those with chemotherapy. However, a significant percentage of patients develop short-term immune-related AEs (irAEs) which range from mild (~70%) to severe cases (~13%) that can lead to modifications of the checkpoint inhibitor therapy and in some cases, death. While some studies have investigated immune mechanisms behind the development of irAEs, much more research is needed to understand the mechanisms and to develop interventions that could attenuate severe irAEs, while maintaining the anti-tumor response intact. Moreover, studies to identify biomarkers that can predict the likelihood of a patient developing severe irAEs would be of great clinical importance. Here we discuss some of the clinical ramifications of irAEs, potential immune mechanisms behind their development and studies that have investigated potentially useful biomarkers of irAEs development.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":"ltac008"},"PeriodicalIF":0.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40687874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Reduced cytotoxicity by mutation of lysine 590 of Pseudomonas exotoxin can be restored in an optimized, lysine-free immunotoxin. 假单胞菌外毒素赖氨酸590突变降低的细胞毒性可以在优化的无赖氨酸免疫毒素中恢复。

Immunotherapy advances Pub Date : 2022-02-21 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac007

A Ammon, L Mellenthin, C Emmerich, E Naschberger, M Stürzl, A Mackensen, F Müller

{"title":"Reduced cytotoxicity by mutation of lysine 590 of Pseudomonas exotoxin can be restored in an optimized, lysine-free immunotoxin.","authors":"A Ammon, L Mellenthin, C Emmerich, E Naschberger, M Stürzl, A Mackensen, F Müller","doi":"10.1093/immadv/ltac007","DOIUrl":"https://doi.org/10.1093/immadv/ltac007","url":null,"abstract":"Immunotoxins, which are fusion proteins of an antibody fragment and a fragment of a bacterial or a plant toxin, induce apoptosis in target cells by inhibition of protein synthesis. ADP-ribosylating toxins often have few lysine residues in their catalytic domain. As they are the target for ubiquitination, the low number of lysines possibly prevents ubiquitin-dependent degradation of the toxin in the cytosol. To reduce this potential degradation, we aimed to generate a lysine-free (noK), Pseudomonas exotoxin (PE)-based immunotoxin. The new generation 24 kDa PE, which lacks all but the furin-cleavage site of domain II, was mutated at lysine 590 (K590) and at K606 in a CD22-targeting immunotoxin and activity was determined against various B cell malignancies in vitro and in vivo. On average, K590 mutated to arginine (R) reduced cytotoxicity by 1.3-fold and K606R enhanced cytotoxicity by 1.3-fold compared to wild type (wt). Mutating K590 to histidine or deleting K590 did not prevent this loss in cytotoxicity. Neither stability nor internalization rate of K590R could explain reduced cytotoxicity. These results highlight the relevance of lysine 590 for PE intoxication. In line with in vitro results, the K606R mutant was more than 1.8-fold more active than the other variants in vivo suggesting that this single mutation may be beneficial when targeting CD22-positive malignancies. Finally, reduced cytotoxicity by K590R was compensated for by K606R and the resulting lysine-free variant achieved wt-like activity in vitro and in vivo. Thus, PE24-noK may represent a promising candidate for down-stream applications that would interfere with lysines.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":"ltac007"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

New and emerging concepts and therapies for the treatment of food allergy 治疗食物过敏的新概念和新疗法

Immunotherapy advances Pub Date : 2022-02-04 DOI: 10.1093/immadv/ltac006

David W Hwang, C. Nagler, C. Ciaccio

引用次数: 3

Peanut oral immunotherapy: current trends in clinical trials. 花生口服免疫疗法:临床试验的当前趋势。

Immunotherapy advances Pub Date : 2022-01-31 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac004

Simone Reinwald, Jennifer M Rolland, Robyn E O'Hehir, Menno C van Zelm

{"title":"Peanut oral immunotherapy: current trends in clinical trials.","authors":"Simone Reinwald, Jennifer M Rolland, Robyn E O'Hehir, Menno C van Zelm","doi":"10.1093/immadv/ltac004","DOIUrl":"https://doi.org/10.1093/immadv/ltac004","url":null,"abstract":"Immunotherapy for allergy has been practiced for over 100 years. Low-dose repeated exposure to specific allergen extracts over several months to years can successfully induce clinical tolerance in patients with allergy to insect venoms, pollen, house dust mite, and domestic animals. Different regimens and routes for immunotherapy include subcutaneous, sublingual, oral, and intralymphatic. Food allergies have been difficult to treat in this way due to high anaphylactic potential and only recently the first immunotherapy for peanut allergy has received regulatory approval. Several clinical trials have indicated high efficacy in desensitisation of peanut-allergic individuals using oral immunotherapy, which allows for safer administration of relatively high allergen concentrations. Still, the risk of adverse events including serious allergic reactions and high anxiety levels for patients remains, demonstrating the need for further optimisation of treatment protocols. Here we discuss the design and outcomes of recent clinical trials with traditional oral immunotherapy, and consider alternative protocols and formulations for safer and more effective oral treatment strategies for peanut allergy.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":"ltac004"},"PeriodicalIF":0.0,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes. 使用金纳米颗粒结合胰岛素原肽并通过空心微针给药作为1型糖尿病的免疫治疗的安全性

Immunotherapy advances Pub Date : 2022-01-27 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac002

D Tatovic, M A McAteer, J Barry, A Barrientos, K Rodríguez Terradillos, I Perera, E Kochba, Y Levin, M Dul, S A Coulman, J C Birchall, C von Ruhland, A Howell, R Stenson, M Alhadj Ali, S D Luzio, G Dunseath, W Y Cheung, G Holland, K May, J R Ingram, M M U Chowdhury, F S Wong, R Casas, C Dayan, J Ludvigsson

{"title":"Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.","authors":"D Tatovic, M A McAteer, J Barry, A Barrientos, K Rodríguez Terradillos, I Perera, E Kochba, Y Levin, M Dul, S A Coulman, J C Birchall, C von Ruhland, A Howell, R Stenson, M Alhadj Ali, S D Luzio, G Dunseath, W Y Cheung, G Holland, K May, J R Ingram, M M U Chowdhury, F S Wong, R Casas, C Dayan, J Ludvigsson","doi":"10.1093/immadv/ltac002","DOIUrl":"https://doi.org/10.1093/immadv/ltac002","url":null,"abstract":"Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":" ","pages":"ltac002"},"PeriodicalIF":0.0,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/e2/ltac002.PMC9327128.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10