{"title":"Harnessing natural killer cell effector function against cancer","authors":"Matthew D. Blunt, S. Khakoo","doi":"10.1093/immadv/ltad031","DOIUrl":"https://doi.org/10.1093/immadv/ltad031","url":null,"abstract":"\u0000 Natural killer (NK) cells are cytotoxic innate lymphoid cells that participate in anti-tumour and anti-viral immune responses. Their ability to rapidly destroy abnormal cells and to enhance the anti-cancer function of dendritic cells, CD8+ T cells and macrophages makes them an attractive target for immunotherapeutic strategies. The development of approaches which augment NK cell activation against cancer is currently under intense preclinical and clinical research and strategies include chimeric antigen receptor (CAR) NK cells, NK cell engagers, cytokines, and immune checkpoint inhibitors. In this review, we highlight recent advances in NK cell therapeutic development and discuss their potential to add to our armamentarium against cancer.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138950993","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}
Immunotherapy advancesPub Date : 2023-12-11eCollection Date: 2024-01-01DOI: 10.1093/immadv/ltad028
J Guillaume, A Perzolli, M Boes
{"title":"Strategies to overcome low MHC-I expression in paediatric and adult tumours.","authors":"J Guillaume, A Perzolli, M Boes","doi":"10.1093/immadv/ltad028","DOIUrl":"10.1093/immadv/ltad028","url":null,"abstract":"<p><p>Immunotherapy has made significant advancements in cancer treatments, improving patients' survival rates and quality of life. Several challenges still need to be addressed, which include the considerable fraction of incomplete curative responses in cancer patients, the development of therapy resistance by tumours, and the occurrence of adverse effects, such as inflammatory and autoimmune complications. Paediatric tumours usually exhibit lower responsiveness to immunotherapies compared to adult tumours. Although the underlying reasons are not yet fully understood, one known mechanism by which tumours avoid immune recognition is through reduced cell surface expression of major histocompatibility complex class I (MHC-I) complexes. Accordingly, the reduced presentation of neoantigens by MHC-I hinders the recognition and targeting of tumour cells by CD8+ T cells, impeding T-cell-mediated cytotoxic anti-tumour responses. MHC-I downregulation indeed often correlates with a poorer prognosis and diminished response to immunotherapy. Understanding the mechanisms underlying MHC-I downregulation in different types of paediatric and adult tumours is crucial for developing strategies to restore MHC-I expression and enhance anti-tumour immune responses. We here discuss progress in MHC-I-based immunotherapies against cancers.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltad028"},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466971","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}
Shuya Kaneko, Fumiaki Sakura, Kay Tanita, A. Shimbo, R. Nambu, Masashi Yoshida, Shuichiro Umetsu, A. Inui, Chizuru Okada, M. Tsumura, Mamiko Yamada, Hisato Suzuki, K. Kosaki, Osamu Ohara, M. Shimizu, Tomohiro Morio, Satoshi Okada, H. Kanegane
{"title":"Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function","authors":"Shuya Kaneko, Fumiaki Sakura, Kay Tanita, A. Shimbo, R. Nambu, Masashi Yoshida, Shuichiro Umetsu, A. Inui, Chizuru Okada, M. Tsumura, Mamiko Yamada, Hisato Suzuki, K. Kosaki, Osamu Ohara, M. Shimizu, Tomohiro Morio, Satoshi Okada, H. Kanegane","doi":"10.1093/immadv/ltad027","DOIUrl":"https://doi.org/10.1093/immadv/ltad027","url":null,"abstract":"Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene is an inborn error of immunity presenting with autoimmunity and lymphoproliferation. Symptoms can vary widely, and no effective treatment has been established. This study investigated the efficacy of Janus kinase (JAK) inhibitors (JAKi) in patients with STAT3-GOF. Four patients were enrolled and their clinical symptoms before and after the initiation of treatment with JAKi were described. A cell stimulation assay was performed using Epstein-Barr virus transformed lymphoid cell lines (EBV-LCLs) that were derived from the patients with STAT3-GOF. The patients presented with various symptoms, and these symptoms were mostly improved after the initiation of JAKi treatment. Upon interleukin-6 stimulation, the EBV-LCLs of patients showed enhanced STAT3 phosphorylation compare with those of the EBV-LCLs of healthy controls. In conclusion, four Japanese patients with STAT3-GOF were successfully treated with JAKi. JAKi ameliorated various symptoms and therefore, the use of JAKi could be an effective treatment option for patients with STAT3-GOF.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"18 2-3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139240349","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}
Immunotherapy advancesPub Date : 2023-11-22eCollection Date: 2023-01-01DOI: 10.1093/immadv/ltad026
Katie R Flaherty, Stephanie Kucykowicz, Johannes Schroth, Will Traves, Kyle T Mincham, George E Finney
{"title":"Efficacy of PD-1 checkpoint inhibitor therapy in melanoma and beyond: are peripheral T cell phenotypes the key?","authors":"Katie R Flaherty, Stephanie Kucykowicz, Johannes Schroth, Will Traves, Kyle T Mincham, George E Finney","doi":"10.1093/immadv/ltad026","DOIUrl":"https://doi.org/10.1093/immadv/ltad026","url":null,"abstract":"Summary Immunotherapy treatment strategies have proven effective in a limited portion of patients, where identifying responders from non-responders to treatment remains a challenge. While some indications can be drawn from invasive biopsies, we need more accessible methods for predicting response and better correlates of response prior to starting therapy. Recent work has identified differences in immune composition at baseline in peripheral blood from melanoma patients responding to PD-1 blockade treatment. Through flow cytometric analysis of T cell receptors, phenotypical features of CD8+ and CD4+ T cells and Tregs could allow for the stratification of treatment response. Analysing T cells within peripheral blood could potentially allow for the stratification of PD-1 treatment response prior to therapy in different cancer settings.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad026"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464788","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}
{"title":"DC-targeting Lentivectors for Cancer Immunotherapy","authors":"Ester Gea-Mallorquí, Sarah Rowland-Jones","doi":"10.1093/immadv/ltad023","DOIUrl":"https://doi.org/10.1093/immadv/ltad023","url":null,"abstract":"Abstract Lentivectors (LVs) induce sustained transgene expression and are attractive vaccine platforms for complex immune scenarios like cancer and persistent infections. This review summarises the literature on lentivectors with potential uses for in vivo immunotherapy, focusing on those targeting the most potent antigen-presenting cells: dendritic cells (DCs). There is a growing interest in myeloid-targeting therapies as, by influencing an early stage in the immune hierarchy, they can orchestrate a more diverse and complex targeted immune response. We dissect the nature of DC-targeting LVs and their induced immune responses to understand the state of the art, identify the knowledge gaps and guide efforts to maximise the generation of potent and effective immune responses. Lentivector-based vaccines provide several advantages over other vaccine platforms, such as directed tropism and limited vector immunogenicity, and have been shown to generate effective and sustained immune responses. Overall, DC-targeting lentivectors stand out as promising tools to be exploited in cancer immunotherapy, and new-generation LVs can further exploit the gained knowledge in the study of naturally-occurring lentiviruses for a more directed and adjuvanted response.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510226","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}
Immunotherapy advancesPub Date : 2023-10-25eCollection Date: 2023-01-01DOI: 10.1093/immadv/ltad021
Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
{"title":"Time to treat the climate and nature crisis as one indivisible global health emergency.","authors":"Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski","doi":"10.1093/immadv/ltad021","DOIUrl":"https://doi.org/10.1093/immadv/ltad021","url":null,"abstract":"","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad021"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415802","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}
Patrícia Silva Santos Ribeiro, Hanneke L D M Willemen, Sabine Versteeg, Christian Martin Gil, Niels Eijkelkamp
{"title":"NLRP3 inflammasome activation in sensory neurons promotes chronic inflammatory and osteoarthritis pain","authors":"Patrícia Silva Santos Ribeiro, Hanneke L D M Willemen, Sabine Versteeg, Christian Martin Gil, Niels Eijkelkamp","doi":"10.1093/immadv/ltad022","DOIUrl":"https://doi.org/10.1093/immadv/ltad022","url":null,"abstract":"Abstract Pain is one of the most debilitating symptoms in rheumatic diseases. Pain often persists after total knee replacement in osteoarthritis, or when inflammation is minimal/absent in rheumatoid arthritis. This suggests that pain transitions to a chronic state independent of the original damage/inflammation. Mitochondrial dysfunction in the nervous system promotes chronic pain and is linked to NLRP3 inflammasome activation. Therefore, we investigated the role of mitochondrial dysfunction and NLRP3 inflammasome activation in the transition from acute to persistent inflammation-induced nociplastic pain and in persistent monoiodoacetate-induced osteoarthritis pain. Intraplantar injection of carrageenan in mice induced transient inflammatory pain that resolved within 7 days. A subsequent intraplantar PGE2 injection induced persistent mechanical hypersensitivity, while in naive mice it resolved within one day. Thus, this initial transient inflammation induced maladaptive nociceptor neuroplasticity, so-called hyperalgesic priming. At day 7, when mice were primed, expression of NLRP3 inflammasome pathway components were increased, and dorsal root ganglia neurons displayed signs of activated NLRP3 inflammasome. Inhibition of NLRP3 inflammasome with MCC950 prevented the transition from acute to chronic pain in this hyperalgesic priming model. In mice with persistent monoiodoacetate-induced osteoarthritis pain, neurons displayed signs of mitochondrial oxidative stress and NLRP3 inflammasome activation. Blocking NLRP3 inflammasome activity attenuated established osteoarthritis pain. In males, NLPR3 inhibition had longer lasting effects than in females. Overall, these data suggest that NLRP3 inflammasome activation in sensory neurons, potentially caused by neuronal oxidative stress, promotes development of persistent inflammatory and osteoarthritis pain. Therefore, targeting NLRP3 inflammasome pathway may be a promising approach to treat chronic pain.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"19 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135266361","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}
Immunotherapy advancesPub Date : 2023-10-12eCollection Date: 2023-01-01DOI: 10.1093/immadv/ltad019
{"title":"Correction to: Blockade of innate inflammatory cytokines TNFα, IL-1β, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression.","authors":"","doi":"10.1093/immadv/ltad019","DOIUrl":"10.1093/immadv/ltad019","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/immadv/ltad011.].</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad019"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241802","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}
Immunotherapy advancesPub Date : 2023-10-12eCollection Date: 2023-01-01DOI: 10.1093/immadv/ltad017
{"title":"Correction to: Immunology of allergen immunotherapy.","authors":"","doi":"10.1093/immadv/ltad017","DOIUrl":"10.1093/immadv/ltad017","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/immadv/ltac022.].</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad017"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241803","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}