Journal of cellular immunology最新文献

{"title":"Estrogen Receptor Alpha Contributes to Intestinal Inflammation in a Murine Model of Ileitis.","authors":"Alyssia V Broncano, Wendy A Goodman","doi":"10.33696/immunology.7.232","DOIUrl":"10.33696/immunology.7.232","url":null,"abstract":"","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"7 4","pages":"127-132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12680021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703243","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":"Mechanisms and Therapeutic Strategies to Overcome Immune Checkpoint Inhibitor Resistance in Melanoma, Head and Neck, and Triple-Negative Breast Cancers.","authors":"Iryna Voloshyna, Apoorvi Tyagi, Stanzin Idga, Nicole Wang, Tazrif Amin, Madonna Hanna, Adil Mukhtar, Francesca Torres, Farah Kabir, Dominic Florian, Chloe Wang, Yury Patskovsky, Michelle Krogsgaard","doi":"10.33696/immunology.7.235","DOIUrl":"10.33696/immunology.7.235","url":null,"abstract":"<p><p>Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment by harnessing the host immune system to target malignancies. Melanoma, head and neck squamous cell carcinoma (HNSCC), and triple-negative breast cancer (TNBC) were among the first solid tumors to gain regulatory approval for ICIs due to their immunogenicity and unmet clinical needs. Melanoma exemplifies the success of ICI therapy, with durable responses driven by its high mutation burden and neoantigen landscape, yet both primary and acquired resistance remain major challenges. In contrast, HNSCC demonstrates clinically meaningful but modest responses in the context of a highly immunosuppressive tumor microenvironment, while TNBC derives limited benefit from ICI, often requiring combination strategies to achieve efficacy. Resistance to ICIs arises from complex tumor-intrinsic, microenvironmental, and systemic mechanisms that collectively undermine effective anti-tumor immunity. This review highlights both shared and cancer-specific mechanisms of ICI resistance across melanoma, TNBC and HNSCC. We also discuss emerging strategies, including combination therapies, neoantigen-based vaccines, adoptive T cell therapies, and precision oncology approaches, to overcome resistance and improve clinical outcomes. Together, these insights provide a framework for optimizing immunotherapy and advance durable benefit in these challenging malignancies.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"7 4","pages":"146-172"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379714","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":"Modeling <i>TCIRG1</i> Neutropenia by Utilizing Patient Derived Induced Pluripotent Stem Cells.","authors":"Vahagn Makaryan, Merideth L Kelley, Audrey Anna Bolyard, Chris Cavanaugh, Jennifer Hesson, Julie Mathieu, Michael J Lenaeus, David C Dale","doi":"10.33696/immunology.7.228","DOIUrl":"10.33696/immunology.7.228","url":null,"abstract":"<p><p>Congenital neutropenia is characterized by a reduced neutrophil count, decreased innate immunity and increased susceptibility to recurrent infections. While congenital neutropenia has various genetic causes, recent studies have linked <i>TCIRG1</i> mutations to this condition. <i>TCIRG1</i>, a key component of the vacuolar ATPase (V-ATPase) complex, is essential for osteoclast function, but its role in hematopoiesis remains unclear. We previously identified heterozygous <i>TCIRG1</i> mutations, including R736S, R736C, R736P, and E722D, in individuals with congenital neutropenia. However, the mechanism by which these mutations lead to impaired granulopoiesis remains unknown. To investigate the functional consequences of <i>TCIRG1</i> mutations, we generated induced pluripotent stem cells (iPSCs) from affected individuals and healthy controls. Using <i>in vitro</i> differentiation protocols, we assessed hematopoietic progenitor formation, proliferation, survival, and neutrophil differentiation. We observed significant defects in myeloid differentiation and increased cell death in patient-derived iPSC lines. CRISPR/Cas9-mediated correction of the R736C mutation restored normal neutrophil differentiation, confirming its pathogenic role. Immunofluorescence analysis revealed reduced expression and altered intracellular localization of the <i>TCIRG1</i> protein, characterized by a more diffuse cytosolic distribution in the mutant cell lines. Our findings suggest that <i>TCIRG1</i> mutations impair neutrophil development, likely through structural and functional disruption of the V-ATPase complex. This study provides new insights into the molecular basis of <i>TCIRG1</i>-associated neutropenia and highlights potential avenues for therapeutic intervention.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"7 3","pages":"98-112"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082738","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":"Personalized Neoantigen DNA Cancer Vaccines: Current Status and Future Perspectives","authors":"Nadia Viborg, Daniela Kleine-Kohlbrecher, Birgitte Rønø","doi":"10.33696/immunology.6.188","DOIUrl":"https://doi.org/10.33696/immunology.6.188","url":null,"abstract":"Tumor mutation-derived neoantigens are considered promising targets for cancer immunotherapy. Personalized vaccines have emerged as an approach to deliver neoantigens and thereby trigger the induction of specific T-cell responses that can find and eliminate tumor cells based on the cell-surface presence of neoantigens. To this end, several neoantigen vaccine formats have provided encouraging results in clinical trials, resulting in neoantigen immunogenicity and clinical benefit. DNA offers a versatile and safe platform to deliver neoantigens and immune stimulants in a single entity through vaccination. Herein, we provide an overview of how DNA vaccines are being used as a means to deliver personalized neoantigens to cancer patients. We summarize the developments in DNA vaccine formulation and delivery technologies that contribute to elicit robust immune responses after vaccination. We outline the main results from central preclinical and clinical investigations, showing that neoantigen DNA vaccines induce a specific immune response directed against tumor neoantigens. Lastly, we discuss the opportunities and challenges for neoantigen DNA vaccines as an individualized approach to immunotherapy of cancer.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140362388","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}

{"title":"Cytoreductive Nephrectomy Following Immunotherapy: Evolution, Pearls, and Pitfalls of Treatment.","authors":"Laura E Davis, Adam Calaway, Eric A Singer, Shawn Dason","doi":"10.33696/immunology.6.202","DOIUrl":"10.33696/immunology.6.202","url":null,"abstract":"<p><strong>Introduction: </strong>Renal Cell Carcinoma (RCC) is among the most frequently diagnosed malignancies in both genders with over 81,000 estimated cases in 2024. Despite increasing incidence of renal cell carcinomas <4 cm, up to 1/3 of patients diagnosed with RCC exhibit metastatic disease (mRCC) at time of diagnosis. Cytoreductive nephrectomy (CN), a procedure which encompasses the surgical removal of the primary tumor in patients with metastatic disease, was offered upfront as standard of care during the cytokine era; however, as systemic treatment has evolved, the role of CN in mRCC patients has become less clear.</p><p><strong>Purpose of review: </strong>We sought to review the evolution of CN in mRCC patients from historical treatments through current standard of care considering ongoing clinical trials and perioperative considerations for CN in patients treated with tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI).</p><p><strong>Conclusion: </strong>CN following immunotherapy is safe and beneficial in appropriately selected patients. The choice to perform CN in patients with mRCC amidst an ever-changing treatment landscape is nuanced. Clinical trial enrollment is critical to refine selection criteria and timing of CN. As treatment options continue to progress, shared decision-making and multidisciplinary collaboration remain paramount in selecting the optimal treatment course for each patient.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 4","pages":"163-170"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878792","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":"Development of a Chikungunya Arthritis Disease Activity Score (CHIK-DAS) Based on a Prospective Cohort Study.","authors":"Aileen Y Chang, Samuel Simmens, Hugh Watson, Richard L Amdur, André Siqueira, Abigale Proctor, Sarah Tritsch, Carlos Andres Herrera Gomez, Liliana Encinales, Alfonso Sucerquia Hernández, Jose Forero-Mejía, Alejandro Jaller, Juan Jose Jaller, J Kennedy Amaral, Ilana Heckler, Gary L Simon, Larry Moreland, Andres Cadena, Gary S Firestein","doi":"10.33696/immunology.6.211","DOIUrl":"10.33696/immunology.6.211","url":null,"abstract":"<p><strong>Objective: </strong>Chikungunya virus is spread by mosquitos and causes a debilitating chronic arthritis that has no standard treatment to date and no specific measures of disease activity. The objective of this expert group was to develop a measure of chikungunya arthritis that would be useful for clinical trials and patient care.</p><p><strong>Methods: </strong>A group of rheumatologists and biostatisticians experienced in the clinical and pathological mechanisms of chikungunya evaluated component measures for inclusion in a chikungunya arthritis disease activity score (CHIK-DAS). Utilizing data from a Colombian cohort of 158 chikungunya arthritis patients, linear regression identified components that were independently associated with patient reported outcomes assessing disability, pain, physical and mental quality of life and mobility. A preliminary instrument was developed using multiple imputation and regression backward selection. Cutoffs for grading disease severity were determined.</p><p><strong>Results: </strong>Stiffness, ankle tenderness, and a 30 tender joint count that included the 28 joints traditionally included in the Disease Activity Score-28 were selected in a regression model predicting a composite of five patient reported outcomes. A CHIK-DAS scoring formula was developed through a weighted combination of these selected variables. In comparison to the DAS-28, the CHIK-DAS had improved predictive value for a composite outcome of disability, pain, physical and mental quality of life and mobility. Disease activity cutoffs were defined for remission (<40), mild (40-49.99), moderate (50-59.99) and severe (60+) disease.</p><p><strong>Conclusion: </strong>The CHIK-DAS is a chikungunya specific measure of disease activity that includes the DAS-28 with the addition of ankle tenderness and a stiffness item that are prominent components of chikungunya arthritis. CHIK-DAS may be used as a specific measure of disease activity in chikungunya arthritis in clinical trials and patient care. This metric needs further validation in additional cohorts.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 6","pages":"236-246"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060311","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":"Can Molecular Biomarkers be Utilized to Determine Appropriate Adjuvant Therapy in Early-Stage Non-Small Cell Lung Cancer (NSCLC)?","authors":"Prashanth Ashok Kumar, Alina Basnet, Stephen Graziano","doi":"10.33696/immunology.6.193","DOIUrl":"10.33696/immunology.6.193","url":null,"abstract":"","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 2","pages":"82-86"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494528","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":"Telling Your Research Story.","authors":"Houmam Araj","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 5","pages":"209-210"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649688","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":"A Natural Metabolite and Inhibitor of the NLRP3 Inflammasome: 4-hydroxynonenal.","authors":"Jinmin Zhang, Bradford C Berk, Chia George Hsu","doi":"10.33696/immunology.6.192","DOIUrl":"10.33696/immunology.6.192","url":null,"abstract":"<p><p>The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, crucial in the innate immune response, is linked to various human diseases. However, the effect of endogenous metabolites, like 4-hydroxynonenal (HNE), on NLRP3 inflammasome activity remains underexplored. Recent research highlights HNE's inhibitory role in NLRP3 inflammasome activation, shedding light on its potential as an endogenous regulator of inflammatory responses. Studies demonstrate that HNE blocks NLRP3 inflammasome-mediated pyroptosis and IL-1β secretion. Additionally, covalent targeting emerges as a common mechanism for inhibiting NLRP3 inflammasome assembly, offering promising avenues for therapeutic intervention. Further investigation is needed to understand the impact of endogenous HNE on NLRP3 inflammasome activation, especially in settings where lipid peroxidation byproducts like HNE are produced. Understanding the intricate interplay between HNE and the NLRP3 inflammasome holds significant potential for unraveling novel therapeutic strategies for inflammatory disorders.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 2","pages":"76-81"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319168","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":"Evaluating the Role of the Renin-angiotensin System in COVID-19: Implications for ACE Inhibitor and ARB Use During SARS-CoV-2 Infection.","authors":"Sarah R Tritsch, Evelyn Mendoza-Torres, Mónica Gómez-Pulido, Jairo Castellar-López, Rebecca Lynch, Carlos Herrera Gomez, Hana Akselrod, Adrienne Poon, Sam Simmens, Christopher N Mores, Gary Simon, Lauren C Ray, Sarah Conway, Aileen Y Chang","doi":"10.33696/immunology.6.213","DOIUrl":"10.33696/immunology.6.213","url":null,"abstract":"<p><p>This study aimed to investigate the role of the renin-angiotensin system (RAS) in COVID-19, particularly focusing on key components such as ACE, ACE2, and their related peptides, angiotensin-(1-7) and angiotensin-(1-9). Using serum samples from healthy controls and both non-severe and severe COVID-19 patients, ELISA assays revealed no significant differences in these RAS components between the groups. In addition, <i>in vitro</i> studies showed no impact of ACE inhibitors or Angiotensin Receptor Blockers (ARB) on cell viability during SARS-CoV-2 infection. These clinical findings suggest that RAS alterations may not be a major factor in COVID-19 severity and the <i>in vitro</i> data support current guidelines, indicating the safety of continuing ACE inhibitors and ARBs in COVID-19 patients without evidence of increased SARS-CoV-2 infectivity in the presence of these compounds. This study highlights the lack of significant changes in key RAS components during COVID-19 in a clinical cohort and provides critical <i>in vitro</i> evidence supporting the continued use of ACE inhibitors and ARBs in treating patients.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"6 6","pages":"255-265"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144891","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}