ImmunoTargets and Therapy最新文献

{"title":"The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.","authors":"Xiang Tang, Jinbin Chen, Wei Peng, Zhoutian Yang, Li Hu, Zhiwei Ye, Yizhen Fu, Dandan Hu, Zhongguo Zhou, Minshan Chen, Yaojun Zhang, Jun-Cheng Wang","doi":"10.2147/ITT.S478685","DOIUrl":"10.2147/ITT.S478685","url":null,"abstract":"<p><strong>Objection: </strong>To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Methods: </strong>In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).</p><p><strong>Results: </strong>Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0-13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, <i>P</i> = 0.69) or OS (HR, 0.71, <i>P</i> = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.</p><p><strong>Conclusion: </strong>Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"559-569"},"PeriodicalIF":6.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547986","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":"Assessing the Prognostic Value of 13 Inflammation-Based Scores in Patients with Unresectable or Advanced Biliary Tract Carcinoma After Immunotherapy.","authors":"Fang Wang, Chang Jiang, Wenzhuo He, Heping Li, Gui-Fang Guo, Lixia Xu","doi":"10.2147/ITT.S471502","DOIUrl":"10.2147/ITT.S471502","url":null,"abstract":"<p><strong>Purpose: </strong>The response of patients with biliary tract carcinoma (BTC) to immunotherapy varies widely, and there is an urgent need for biological indicators. The predictive value of inflammation based score (IBS) for the efficacy of immunotherapy in patients with BTC remains unclear, as the evidence is inconsistent. This study aimed to comprehensively examine the predictive value of IBS in peripheral blood on the survival of BTC patients receiving immunotherapy.</p><p><strong>Patients and methods: </strong>We retrospectively assessed 118 patients with advanced BTC who received anti-PD-1 therapy in the first or second line in two medical centers. The Kaplan-Meier, time-dependent ROC, and Harrell's concordance index (C-index) were applied to analyze the predictive value of 13 reported peripheral blood IBS.</p><p><strong>Results: </strong>All 13 IBS were identified as significant prognostic factors for OS in univariate analysis. Pan-immune-inflammation value (PIV) (p=0.005), PILE (composed of PIV, lactate dehydrogenase and Eastern Cooperative Oncology Group performance status) (<i>p</i>=0.033), neutrophil-to-lymphocyte ratio (NLR) (<i>p</i>=0.003), platelet-to-lymphocyte ratio (PLR) (<i>p</i><0.001), lymphocyte-to-monocyte ratio (LMR) (<i>p</i>=0.006), systemic immune inflammation index (SII) (<i>p</i>=0.039), CRP-to-albumin ratio (CAR) (<i>p</i>=0.025), and Albumin-NLR (<i>p</i>=0.008) were identified as independent prognostic factors for OS in multivariate analysis. PIV and PILE scores were superior to other scores, according to time-dependent ROC curves, and their superiority became more pronounced after the 12-month time point. C-index analysis showed PIV (C-index 0.62, 95% CI: 0.55, 0.68) and PILE (C-index 0.62, 95% CI: 0.55, 0.70), both superior to other IBS.</p><p><strong>Conclusion: </strong>PIV and PILE scores are independent predictors of OS in patients with BTC after immunotherapy and are superior to other IBS. PIV and PILE may be able to help screen out patients with advanced BTC who are less likely to benefit from anti-PD-1 monotherapy. Due to the retrospective nature of this analysis, the predictive value of PIV and PILE require validation in further prospective studies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"541-557"},"PeriodicalIF":6.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476416","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":"Harnessing Variability Signatures and Biological Noise May Enhance Immunotherapies' Efficacy and Act as Novel Biomarkers for Diagnosing and Monitoring Immune-Associated Disorders.","authors":"Tal Sigawi, Adir Israeli, Yaron Ilan","doi":"10.2147/ITT.S477841","DOIUrl":"10.2147/ITT.S477841","url":null,"abstract":"<p><p>Lack of response to immunotherapies poses a significant challenge in treating immune-mediated disorders and cancers. While the mechanisms associated with poor responsiveness are not well defined and change between and among subjects, the current methods for overcoming the loss of response are insufficient. The Constrained Disorder Principle (CDP) explains biological systems based on their inherent variability, bounded by dynamic boundaries that change in response to internal and external perturbations. Inter and intra-subject variability characterize the immune system, making it difficult to provide a single therapeutic regimen to all patients and even the same patients over time. The dynamicity of the immune variability is also a significant challenge for personalizing immunotherapies. The CDP-based second-generation artificial intelligence system is an outcome-based dynamic platform that incorporates personalized variability signatures into the therapeutic regimen and may provide methods for improving the response and overcoming the loss of response to treatments. The signatures of immune variability may also offer a method for identifying new biomarkers for early diagnosis, monitoring immune-related disorders, and evaluating the response to treatments.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"525-539"},"PeriodicalIF":6.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476417","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 Self-Activating IL-15 Chimeric Cytokine Receptor to Empower Cancer Immunotherapy.","authors":"Sumei Chen, Lingrong Yang, Bing Xia, Haitao Zhu, Zhenghao Piao, Youssef Jounaidi","doi":"10.2147/ITT.S490498","DOIUrl":"https://doi.org/10.2147/ITT.S490498","url":null,"abstract":"<p><strong>Background: </strong>Enhancing NK cells' antitumor activity requires sustained cytokine signaling. Interleukin-15 (IL-15) is a potent immunostimulatory cytokine used to armor CAR-NK and CAR-T cell immunotherapies. However, strategies to increase IL-15 expression and antitumor effect may trigger systemic toxicity with the potential to promote oncogenesis and autoimmune diseases.</p><p><strong>Methods: </strong>To overcome these limitations, we developed a new platform (IL15RB) whereby IL-15 with IL-2 signal peptide is tethered to its receptor, IL2Rβ.</p><p><strong>Results: </strong>NK92-expressing IL15RB (NK92^IL15RB) cells expand indefinitely without exogenous cytokines and have significantly higher anticancer activity than NK-92 stimulated by IL-15, IL-2, or expressing tethered IL-2. NK92^IL5RB showed resistance to irradiation and IL-4. However, TGFβ1 substantially reduced NK92^IL5RB killing, suggesting the need to inhibit TGFβ1 in IL-15-mediated immunotherapies. IL15RB induced strong STAT3 but weaker STAT5 and STAT1 activation compared to IL-2. Chronic exposure of NK92^IL15RB cells to cancer cells reduced STAT3 and STAT1 activation irreversibly, suggesting a role in exhaustion. Combination with CAR-CD19 enhanced NK92^IL15RB antitumor activity against leukemia and increased its STAT5 activation. NK92^IL15RB anti-tumors activity was further enhanced by combination with anti-PD1.</p><p><strong>Conclusion: </strong>Our data suggest that the tethering of IL-15 to its receptor IL2Rβ empowers NK cell cytolytic activity. Additionally, the tethering of IL-15 will prevent any systemic risk of toxicity.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"513-524"},"PeriodicalIF":6.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476415","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":"Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2-Negative Metastatic Breast Cancer, Real-World Data from a Low-Resourced Country.","authors":"Hikmat Abdel-Razeq, Baha Sharaf, Suhaib Khater, Huda Jafar Baidoun, Hira Bani Hani, Ayat Taqash, Osama El Khatib, Sarah Edaily, Mahmoud Abunasser, Faris Tamimi, Yosra Nabeel Al-Masri, Tamer Moh'd Waleed Al-Batsh, Anas Zayed, Tala Ghatasheh, Tala Radaideh","doi":"10.2147/ITT.S479153","DOIUrl":"10.2147/ITT.S479153","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC). Here, we present the real-world clinical outcomes and toxicity data of patients treated at a single cancer center.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on patients with HR+/HER2- MBC treated with ribociclib plus endocrine therapy (ET). Outcomes measured included progression-free survival (PFS), overall survival (OS), and adverse events.</p><p><strong>Results: </strong>A total of 356 patients (median age 52, range 27-91 years) were enrolled, all with metastatic disease; 204 (57.5%) had de novo metastasis, and 183 (51.4%) had visceral metastasis. Ribociclib was combined with aromatase inhibitors in 321 patients (90.2%) and with fulvestrant in 35 patients (9.8%). Dose reduction was needed in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzymes (5.9%). After a median follow-up of 36.3 months, median PFS was 27.3 months (95% CI: 21.3-31.7). PFS was significantly better in patients receiving ribociclib as first-line therapy (32.1 months, 95% CI: 27.7-42.1, p < 0.0001) and those with non-visceral metastasis (38.6 months, 95% CI: 29.8-NR, p < 0.0001). Similarly, OS was significantly better in first-line treatment (48.6 months, 95% CI: 39.1-NR) and non-visceral metastasis cases (NR, 95% CI: 40.6-NR, p < 0.0001). No significant differences in 3-year PFS and OS were found between patients with and without dose reductions.</p><p><strong>Conclusion: </strong>In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"501-512"},"PeriodicalIF":6.2,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373103","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":"EPS T14 from <i>Bacillus licheniformis</i> Prevents Infection of Human Nasal Epithelial Cells by Respiratory Viruses.","authors":"Gaetana Pezzino, Alessia Calabrò, Fabiana Drommi, Stefania Campana, Riccardo Cavaliere, Irene Bonaccorsi, Paolo Carrega, Vincenzo Zammuto, Maria Giovanna Rizzo, Concetta Gugliandolo, Guido Ferlazzo, Claudia De Pasquale","doi":"10.2147/ITT.S470319","DOIUrl":"10.2147/ITT.S470319","url":null,"abstract":"<p><strong>Background: </strong>Respiratory viral infections are a leading cause of severe diseases and mortality; therefore, novel treatments effective for their prevention are highly requested. Here, we identified a broad-spectrum antiviral activity of a natural exopolysaccharide, EPS T14, purified from a marine thermotolerant strain of <i>Bacillus licheniformis</i> strain T14.</p><p><strong>Methods: </strong>The effects on human normal nasal epithelial cells (HNEpCs) following treatment with EPS T14 was evaluated at different time points and with increasing concentration of compound. To assess the antiviral properties, viability of HNEpCs treated with EPS T14 was analysed following infection with different respiratory viruses.</p><p><strong>Results: </strong>Neither toxicity nor pro-inflammatory properties were observed in vitro on HNEpCs treated with EPS T14 up to high concentrations, thus ensuring its safety. Cell culture-based assays revealed that treatment of HNEpCs with EPS T14 (used at 400ug/mL) results in efficient prevention of cell infection by different respiratory viruses through physically hindering the entry of the viruses via cell surface receptors. Interestingly, in addition to this prophylactic antiviral activity, EPS T14 also shows a long-lasting efficacy by inhibiting viral spread in the cell culture. Finally, combination of EPS T14 with a hypertonic saline solution shows a synergistic antiviral activity.</p><p><strong>Conclusion: </strong>EPS T14 can exert both prophylactic and therapeutic antiviral activity by blocking viral attachment to cellular receptors and could therefore represent a promising antiviral agent for preventing infections by different respiratory viruses.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"487-499"},"PeriodicalIF":6.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373104","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":"Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated by Prolonged Thrombocytopenia: A Comprehensive Review.","authors":"Abdelrahman Elsayed, Basant Elsayed, Mohamed Elmarasi, Ahmed Adel Elsabagh, Engy Elsayed, Ibrahim Elmakaty, Mohamed Yassin","doi":"10.2147/ITT.S463384","DOIUrl":"https://doi.org/10.2147/ITT.S463384","url":null,"abstract":"<p><p>Hematopoietic cell transplantation (HCT) is a well-established procedure that has become a therapeutic mainstay for various hematological conditions. Prolonged thrombocytopenia following HCT is associated with a significant risk of morbidity and mortality, yet no universally recognized treatment protocol exists for such a complication. First-generation thrombopoietin receptor (TpoR) agonists as well as second-generation agents are known for their role in enhancing platelet production, and their use is expanding across various thrombocytopenic conditions. Therefore, we conducted this comprehensive review of the literature to provide an updated evaluation of the use of TpoR agonists and explore their efficacy and safety in the treatment of extended post-HCT thrombocytopenia. The literature search was conducted using PubMed database from 1996 through December 2023, using a predefined strategy with medical subject headings terms. We identified 64 reports on the utility of TpoR agonists, five of them were randomized controlled trials and the rest were retrospective observational studies and case series, with a total number of 1730 patients. Second-generation TpoR agonists appear more convenient than subcutaneous recombinant human thrombopoietin (rhTpo) as they can be orally administered and exhibit similar efficacy in platelet recovery, as indicated by recent trial results. Among these agents, avatrombopag, unlike eltrombopag, does not require any dietary restrictions, which could be more favorable for patients. However, eltrombopag remains the most extensively studied agent. TpoR agonists had promising effects in the treatment of post-HCT thrombocytopenia with a good safety profile so far, highlighting the potential benefit of their use.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"461-486"},"PeriodicalIF":6.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297094","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":"Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study.","authors":"Murong Wang, Qunfang Zhou, Hui Li, Mingyu Liu, Ruixia Li, Wei Wang, Xiaohui Wang, Jinhua Huang, Feng Duan","doi":"10.2147/ITT.S477972","DOIUrl":"https://doi.org/10.2147/ITT.S477972","url":null,"abstract":"<p><strong>Purpose: </strong>The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis.</p><p><strong>Patients and methods: </strong>A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy.</p><p><strong>Results: </strong>The median OS was 20.1 ± 1.2 (17.7-22.5) months and 15.7 ± 1.5 (12.8-18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49-0.94; <i>P</i> = 0.021) and (HR, 0.66; 95% CI, 0.50-0.87; <i>P</i> = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36-0.90; <i>P</i> = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68-1.80; <i>P</i> = 0.689) was similar between the Len and Len+PD-1 groups without HAIC.</p><p><strong>Conclusion: </strong>Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"447-459"},"PeriodicalIF":6.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11397328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297093","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":"Clinical Significance and Molecular Annotation for PD-L1 Negative Advanced Non-Small Cell Lung Cancer with Sensitivity to Responsive to Dual PD-1/CTLA-4 Blockade.","authors":"Li Wang, Li Liu, Jing Zhao, Xin Yu, Chunxia Su","doi":"10.2147/ITT.S476040","DOIUrl":"https://doi.org/10.2147/ITT.S476040","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients.</p><p><strong>Methods: </strong>In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis.</p><p><strong>Results: </strong>A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy.</p><p><strong>Conclusion: </strong>Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"435-445"},"PeriodicalIF":6.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297092","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":"Revolutionizing Immunotherapy: Unveiling New Horizons, Confronting Challenges, and Navigating Therapeutic Frontiers in CAR-T Cell-Based Gene Therapies.","authors":"Shivani Srivastava, Anuradha Tyagi, Vishakha Anand Pawar, Nawaid Hussain Khan, Kavita Arora, Chaitenya Verma, Vinay Kumar","doi":"10.2147/ITT.S474659","DOIUrl":"10.2147/ITT.S474659","url":null,"abstract":"<p><p>The CAR-T cell therapy has marked the dawn of new era in the cancer therapeutics and cell engineering techniques. The review emphasizes on the challenges that obstruct the therapeutic efficiency caused by cell toxicities, immunosuppressive tumor environment, and decreased T cell infiltration. In the interest of achieving the overall survival (OS) and event-free survival (EFS) of patients, the conceptual background of potential target selection and various CAR-T cell design techniques are described which can minimize the off-target effects, reduce toxicity, and thus increase the resilience of CAR-T cell treatment in the haematological malignancies as well as in solid tumors. Furthermore, it delves into cutting-edge technologies like gene editing and synthetic biology, providing new opportunities to enhance the functionality of CAR-T cells and overcome mechanisms of immune evasion. This review provides a comprehensive understanding of the complex and diverse aspects of CAR-T cell-based gene treatments, including both scientific and clinical aspects. By effectively addressing the obstacles and utilizing the capabilities of cutting-edge technology, CAR-T cell therapy shows potential in fundamentally changing immunotherapy and reshaping the approach to cancer treatment.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"413-433"},"PeriodicalIF":6.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112797","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}