ImmunoTargets and Therapy最新文献

{"title":"A Case of Complete Remission in Proficient Mismatch Repair (pMMR) Advanced Colon Cancer Treated with Sintilimab and XELOX.","authors":"Jiangpeng Zhu,&nbsp;Guangyao Li,&nbsp;Zhengjun Zhang,&nbsp;Yandong Wang","doi":"10.2147/ITT.S393526","DOIUrl":"https://doi.org/10.2147/ITT.S393526","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is the 3rd most common malignant tumors after breast cancer and lung cancer, accounting for 9.4% of patients. Some patients had distant metastasis at the time of diagnosis without surgery opportunity. It is particularly important to prolong patient survival and improve quality of life.</p><p><strong>Patient concerns: </strong>A 73-year-old female was admitted with discomfort over 2 months. Enlarged lymph nodes in the left supraclavicular fossa were observed in chest computed tomography (CT). Enhanced abdominal CT showed thickening of the right colon wall with multiple metastatic lymph nodes in the abdomen. Colonoscopy showed ileocecal mass and pathology showed moderately and poorly differentiated adenocarcinoma. Physical examination showed a 2*2 cm lymph node could be touched in the left supraclavicular fossa. The patient was diagnosed advanced colon cancer by the histopathological examination and imaging findings. Actually, it is hardly to resect radically.</p><p><strong>Intervention: </strong>Sintilimab combined with XELOX was initiated. Two period of treatment after initial therapy, laparoscopic radical resection of right colon cancer was performed successfully.</p><p><strong>Outcomes: </strong>After conversion treatment, the enlarged lymph nodes and primary tumor were significantly reduced. The patient was discharged successfully three weeks after surgery. Both specimen and 14 lymph nodes dissected showed no malignancy in pathology. Tumor regression grading (TRG) is 0, which indicate complete regression with no residual tumor cells including lymph nodes. The patient obtained a pathological complete response (pCR).</p><p><strong>Lessons: </strong>The patient achieved a great therapeutic benefit with the above-mentioned chemotherapy in this case. The case provides a potential reference for pMMR CRC patients treating with immune checkpoint inhibitors (ICIs).</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"17-23"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/bd/itt-12-17.PMC9951411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10792393","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":"Association of Toll-like Receptors 1, 2, 4, 6, 8, 9 and 10 Genes Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Sudanese Patients.","authors":"Najwa A Mhmoud","doi":"10.2147/ITT.S404915","DOIUrl":"https://doi.org/10.2147/ITT.S404915","url":null,"abstract":"<p><strong>Background: </strong>Genetic factors are important contributors to the development of a wide range of complex disease. Polymorphisms in genes encoding for toll-like receptors (TLRs) usually influence the efficiency of the immune response to infection and are associated with disease susceptibility and progression. Therefore, we aim to describe the first association between TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Sudanese patients.</p><p><strong>Methodology: </strong>Here we performed a case study which included 160 tuberculosis patients and 220 healthy matched controls from Sudan. In the study population, we evaluated the possible association between 86 markers in TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to PTB disease in Sudanese population using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).</p><p><strong>Results: </strong>From our results it appeared that in the PTB population the TLR1 (rs5743557, rs4833095, rs5743596), TLR2 (rs5743704, rs5743708, rs3804099), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810), TLR8 (rs3764879, rs3764880), TLR9 (rs352165, rs352167, rs187084) and TLR10 (rs4129009) were significantly more often encountered (p<0.0001) than in the control population and were associated with PTB in the Sudanese population. For the other polymorphisms tested, no association with PTB was found in the population tested.</p><p><strong>Conclusion: </strong>The work describes novel mutations in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9 and TLR10 genes and their association with PTB infection in Sudanese population. These results will enhance our ability to determine the risk of developing the disease by targeting specific TLR pathways to reduce the severity of the disease. Future studies are needed in a larger sample to replicate our findings and understand the mechanism of association of TLR polymorphism in PTB.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"12 ","pages":"47-75"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/0a/itt-12-47.PMC10085002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9304349","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":"Current Strategies in Treating Cytokine Release Syndrome Triggered by Coronavirus SARS-CoV-2.","authors":"Long G Wang, Luxi Wang","doi":"10.2147/ITT.S360151","DOIUrl":"10.2147/ITT.S360151","url":null,"abstract":"<p><p>Since the beginning of the SARS-CoV-2 pandemic, the treatments and management of the deadly COVID-19 disease have made great progress. The strategies for developing novel treatments against COVID-19 include antiviral small molecule drugs, cell and gene therapies, immunomodulators, neutralizing antibodies, and combination therapies. Among them, immunomodulators are the most studied treatments. The small molecule antiviral drugs and immunoregulators are expected to be effective against viral variants of SARS-CoV-2 as these drugs target either conservative parts of the virus or common pathways of inflammation. Although the immunoregulators have shown benefits in reducing mortality of cytokine release syndrome (CRS) triggered by SARS-CoV-2 infections, extensive investigations on this class of treatment to launch novel therapies that substantially improve efficacy and reduce side effects are still warranted. Moreover, great challenges have emerged as the SARS-CoV-2 virus quickly, frequently, and continuously evolved. This review provides an update and summarizes the recent advances in the treatment of COVID-19 and in particular emphasized the strategies in managing CRS triggered by SARS-CoV-2. A brief perspective in the battle against the deadly disease was also provided.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"11 1","pages":"23-35"},"PeriodicalIF":6.2,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47571239","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":"Immunotargets and Therapy for Prurigo Nodularis","authors":"A. Labib, T. Ju, A. Vander Does, G. Yosipovitch","doi":"10.2147/ITT.S316602","DOIUrl":"https://doi.org/10.2147/ITT.S316602","url":null,"abstract":"Abstract Prurigo nodularis is a chronic inflammatory skin disease consisting of severely pruritic nodules that can be very debilitating for patients. The basis of this skin condition is immunological dysregulation and neural amplification, driven by T-lymphocytes, mast cells, eosinophilic granulocytes, macrophages, and cytokines mediating itchy processes. Further complicating this already taxing diagnosis is the lack of approved treatment and consensus on management; although there are off-label treatments utilized as therapy. Immunomodulators are the cornerstone of treatment for PN, and additional novel therapies targeting key players in the immunological cascade are currently undergoing investigation. In this review, we will highlight targets of the immune cascade and explore current immunomodulating treatments as well as immunotherapies on the horizon for the management of prurigo nodularis.","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"11 1","pages":"11 - 21"},"PeriodicalIF":7.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46051410","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":"Immune Checkpoint Blockade for the Treatment of Hodgkin Lymphoma.","authors":"Adam Yuh Lin, Joseph Michael Schnitter, Leo I Gordon","doi":"10.2147/ITT.S284988","DOIUrl":"10.2147/ITT.S284988","url":null,"abstract":"<p><p>Classical Hodgkin lymphoma is biologically different than other lymphomas. The cancer cells only occupy a small amount of the lymph node and evade the immune system by amplification of PD-L1 and PD-L2. Therefore, checkpoint inhibitors are a logical treatment option for Hodgkin lymphoma patients to unlock the immune system. Checkpoint inhibitors have shown high response rates in clinical trials in advanced-stage Hodgkin lymphoma. The two most commonly used checkpoint inhibitors are pembrolizumab and nivolumab, both FDA approved as third-line therapy. There is increasing interest in the use of checkpoint inhibitors with combination chemotherapy or with other targeted agents in the second-line or even frontline setting. In this review, we will highlight the clinical trials that led to approvals of checkpoint inhibitors for Hodgkin lymphoma.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"11 ","pages":"1-10"},"PeriodicalIF":6.2,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/a8/itt-11-1.PMC8882667.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10614150","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":"The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome.","authors":"Jessica D Macdougall,&nbsp;Kevin O Thomas,&nbsp;Onyinye I Iweala","doi":"10.2147/ITT.S276872","DOIUrl":"https://doi.org/10.2147/ITT.S276872","url":null,"abstract":"<p><p>Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains. We review the immune cell populations involved in the sensitization and effector phases of alpha-gal syndrome and describe the current understanding of why allergic responses to ingested alpha-gal can be delayed by several hours. We review the foundation of management in alpha-gal syndrome, namely avoidance, but also discuss the use of antihistamines, mast cell stabilizers, and the emerging role of complementary and alternative therapies, biological products, and oral immunotherapy in the management of this condition. Alpha-gal syndrome influences the safety and tolerability of medications and medical devices containing or derived from mammalian products and impacts quality of life well beyond food choices.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"11 ","pages":"37-54"},"PeriodicalIF":7.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/9f/itt-11-37.PMC9484563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295819","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":"IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity.","authors":"Melissa Maria Johanna van Gool,&nbsp;Marjolein van Egmond","doi":"10.2147/ITT.S266242","DOIUrl":"https://doi.org/10.2147/ITT.S266242","url":null,"abstract":"<p><p>Mucosal surfaces constitute the frontiers of the body and are the biggest barriers of our body for the outside world. Immunoglobulin A (IgA) is the most abundant antibody class present at these sites. It passively contributes to mucosal homeostasis via immune exclusion maintaining a tight balance between tolerating commensals and providing protection against pathogens. Once pathogens have succeeded in invading the epithelial barriers, IgA has an active role in host-pathogen defense by activating myeloid cells through divers receptors, including its Fc receptor, FcαRI (CD89). To evade elimination, several pathogens secrete proteins that interfere with either IgA neutralization or FcαRI-mediated immune responses, emphasizing the importance of IgA-FcαRI interactions in preventing infection. Depending on the IgA form, either anti- or pro-inflammatory responses can be induced. Moreover, the presence of excessive IgA immune complexes can result in continuous FcαRI-mediated activation of myeloid cells, potentially leading to severe tissue damage. On the one hand, enhancing pathogen-specific mucosal and systemic IgA by vaccination may increase protective immunity against infectious diseases. On the other hand, interfering with the IgA-FcαRI axis by monovalent targeting or blocking FcαRI may resolve IgA-induced inflammation and tissue damage. This review describes the multifaceted role of FcαRI as immune regulator between anti- and pro-inflammatory responses of IgA, and addresses potential novel therapeutic strategies that target FcαRI in disease.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"9 ","pages":"351-372"},"PeriodicalIF":7.2,"publicationDate":"2021-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/df/itt-9-351.PMC7801909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38755185","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":"Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?","authors":"Francesco Passiglia,&nbsp;Maria Lucia Reale,&nbsp;Valeria Cetoretta,&nbsp;Silvia Novello","doi":"10.2147/ITT.S253581","DOIUrl":"https://doi.org/10.2147/ITT.S253581","url":null,"abstract":"<p><p>The therapeutic targeting of the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis marked a milestone in the treatment of non-small cell lung cancer (NSCLC), leading to unprecedented response duration and long-term survival for a relevant subgroup of patients affected by non-oncogene-addicted, metastatic disease. However, the biological heterogeneity as well as the occurrence of innate/acquired resistance are well-known phenomena which significantly affect the therapeutic response to immunotherapy. To date, we are moving towards the second phase of the \"immune-revolution\", characterized by the advent of new immune-checkpoint inhibitors combinations, aiming to target the main resistance pathways and ultimately increase the number of NSCLC patients who may derive long-term clinical benefit from immunotherapy. In this review, we provide an updated and comprehensive overview of the main PD-1/PD-L1 inhibitors' combination approaches under clinical investigation in non-oncogene addicted, metastatic NSCLC patients, including checkpoints (other than CTLA-4) as well as \"immune-metabolism\" modulators, DNA repair pathway inhibitors, antiangiogenic agents, cytokines, and a new generation of vaccines, with the final aim of identifying the most promising options on the horizon.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"10 ","pages":"9-26"},"PeriodicalIF":7.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/fb/itt-10-9.PMC7872895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10344101","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":"Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery.","authors":"Alexander P Horkowitz,&nbsp;Ashley V Schwartz,&nbsp;Carlos A Alvarez,&nbsp;Edgar B Herrera,&nbsp;Marilyn L Thoman,&nbsp;Dale A Chatfield,&nbsp;Kent G Osborn,&nbsp;Ralph Feuer,&nbsp;Uduak Z George,&nbsp;Joy A Phillips","doi":"10.2147/ITT.S279228","DOIUrl":"https://doi.org/10.2147/ITT.S279228","url":null,"abstract":"<p><strong>Introduction: </strong>This study was designed to explore the role of acetylcholine (ACh) in pulmonary viral infection and recovery. Inflammatory control is critical to recovery from respiratory viral infection. ACh secreted from non-neuronal sources, including lymphocytes, plays an important, albeit underappreciated, role in regulating immune-mediated inflammation.</p><p><strong>Methods: </strong>ACh and lymphocyte cholinergic status in the lungs were measured over the course of influenza infection and recovery. The role of ACh was examined by inhibiting ACh synthesis in vivo. Pulmonary inflammation was monitored by Iba1 immunofluorescence, using a novel automated algorithm. Tissue repair was monitored histologically.</p><p><strong>Results: </strong>Pulmonary ACh remained constant through the early stage of infection and increased during the peak of the acquired immune response. As the concentration of ACh increased, cholinergic lymphocytes appeared in the BAL and lungs. Cholinergic capacity was found primarily in CD4 T cells, but also in B cells and CD8 T cells. The cholinergic CD4⁺ T cells bound to influenza-specific tetramers and were retained in the resident memory regions of the lung up to 2 months after infection. Histologically, cholinergic lymphocytes were found in direct physical contact with activated macrophages throughout the lung. Inflammation was monitored by ionized calcium-binding adapter molecule 1 (Iba1) immunofluorescence, using a novel automated algorithm. When ACh production was inhibited, mice exhibited increased tissue inflammation and delayed recovery. Histologic examination revealed abnormal tissue repair when ACh was limited.</p><p><strong>Conclusion: </strong>These findings point to a previously unrecognized role for ACh in the transition from active immunity to recovery and pulmonary repair following respiratory viral infection.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"9 ","pages":"333-350"},"PeriodicalIF":7.2,"publicationDate":"2020-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/9b/itt-9-333.PMC7751717.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39088816","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":"Complement Inhibition for the Treatment of Myasthenia Gravis.","authors":"Renato Mantegazza, Fiammetta Vanoli, Rita Frangiamore, Paola Cavalcante","doi":"10.2147/ITT.S261414","DOIUrl":"10.2147/ITT.S261414","url":null,"abstract":"<p><p>Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Approximately 80-90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR). A major drive of AChR antibody-positive MG pathology is represented by complement activation. The role of the complement cascade has been largely demonstrated in patients and in MG animal models. Complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChR. Given that the complement system works as an activation cascade, there are many potential targets that can be considered for therapeutic intervention. Preclinical studies have confirmed the efficacy of complement inhibition in ameliorating MG symptoms. Eculizumab, an antibody directed towards C5, has recently been approved for the treatment of AChR antibody-positive gMG. Other complement inhibitors, targeting C5 as well, are currently under phase III study. Complement inhibitors, however, may present prohibitive costs. Therefore, the identification of a subset of patients more or less prone to respond to such therapies would be beneficial. For such purpose, there is a critical need to identify possible biomarkers predictive of therapeutic response, a field not yet sufficiently explored in MG. This review aims to give an overview of the complement cascade involvement in MG, the evolution of complement-inhibiting therapies and possible biomarkers useful to tailor and monitor complement-directed therapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"9 ","pages":"317-331"},"PeriodicalIF":7.2,"publicationDate":"2020-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/61/itt-9-317.PMC7751298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39088815","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}