Journal of Immunotherapy最新文献_第5页

Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy. 纳武单抗免疫治疗继发的多发发疹性角膜棘瘤。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-04-01 Epub Date: 2023-11-27 DOI: 10.1097/CJI.0000000000000498

Eric Olsen, Steven A Svoboda, Marjorie Montanez-Wiscovich, Sami K Saikaly

引用次数: 0

Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments. 抑制活化淋巴细胞中表达的 PTPN3 可增强头颈癌中抗 PD-1 疗法的抗肿瘤效果，尤其是在缺氧环境中。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-04-01 Epub Date: 2024-02-01 DOI: 10.1097/CJI.0000000000000503

Shogo Masuda, Hideya Onishi, Naoya Iwamoto, Akira Imaizumi, Satoko Koga, Shinjiro Nagao, Keita Sakanashi, Shinsaku Itoyama, Akiko Fujimura, Noritaka Komune, Ryunosuke Kogo, Masayo Umebayashi, Takashi Morisaki, Takashi Nakagawa

{"title":"Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments.","authors":"Shogo Masuda, Hideya Onishi, Naoya Iwamoto, Akira Imaizumi, Satoko Koga, Shinjiro Nagao, Keita Sakanashi, Shinsaku Itoyama, Akiko Fujimura, Noritaka Komune, Ryunosuke Kogo, Masayo Umebayashi, Takashi Morisaki, Takashi Nakagawa","doi":"10.1097/CJI.0000000000000503","DOIUrl":"10.1097/CJI.0000000000000503","url":null,"abstract":"In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"89-97"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host. 以 Mucin-1 为靶点的嵌合抗原受体 T 细胞能有效、安全地控制免疫功能正常宿主的实体瘤。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-04-01 Epub Date: 2024-01-25 DOI: 10.1097/CJI.0000000000000505

Ru Zhou, Shu-Ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, Pinku Mukherjee

{"title":"Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host.","authors":"Ru Zhou, Shu-Ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, Pinku Mukherjee","doi":"10.1097/CJI.0000000000000505","DOIUrl":"10.1097/CJI.0000000000000505","url":null,"abstract":"The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related efficacies and toxicities may have been missed. In this study, we engineered syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1) and tested the MUC1 CAR T cells' efficacy and toxicity in the immunocompetent human MUC1-expressing mouse models. The MUC1 CAR T cells significantly eliminated murine pancreatic and breast cancer cell lines in vitro. In vivo, MUC1 CAR T cells significantly slowed the mammary gland tumor progression in the spontaneous PyVMT×MUC1.Tg (MMT) mice, prevented lung metastasis, and prolonged survival. Most importantly, there was minimal short or long-term toxicity with acceptable levels of transient liver toxicity but no kidney toxicity. In addition, the mice did not show any signs of weight loss or other behavioral changes with the treatment. We also report that a single dose of MUC1 CAR T-cell treatment modestly reduced the pancreatic tumor burden in a syngeneic orthotopic model of pancreatic ductal adenocarcinoma given at late stage of an established tumor. Taken together, these findings suggested the further development of tMUC1-targeted CAR T cells as an effective and relatively safe treatment modality for various tMUC1-expressing solid tumors.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"77-88"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathologic Complete Response After Gastric Artery Chemoembolization Combined With Tislelizumab for Neoadjuvant Therapy of Locally Advanced Gastric Cancer: A Case Report. 胃动脉化疗栓塞联合替利单抗新辅助治疗局部晚期胃癌病理完全缓解1例

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-04-01 Epub Date: 2023-11-23 DOI: 10.1097/CJI.0000000000000488

Yufu Lin, Yabo Chen, Shenggan Lin, Jingmei Zheng, Xiuping Zhang, Lu Gan

{"title":"Pathologic Complete Response After Gastric Artery Chemoembolization Combined With Tislelizumab for Neoadjuvant Therapy of Locally Advanced Gastric Cancer: A Case Report.","authors":"Yufu Lin, Yabo Chen, Shenggan Lin, Jingmei Zheng, Xiuping Zhang, Lu Gan","doi":"10.1097/CJI.0000000000000488","DOIUrl":"10.1097/CJI.0000000000000488","url":null,"abstract":"Gastric cancer is the most common type of gastrointestinal cancer in China which about 80% of patients are locally advanced or advanced when diagnosed. Surgery along brings high recurrence rate for locally advanced gastric cancer (LAGC), and neoadjuvant therapies are needed. The use of programmed cell death-1 (PD-1)/programmed death-ligand 1 inhibitor nowadays improved the disease-free survival for LAGC, however, only <35% of patients achieved pathologic complete response (pCR) after neoadjuvant therapy nowadays. Therefore, new regimens are needed to be investigated. Gastric artery chemoembolization is applied to metastasis gastric cancer and researches showed interventional therapy can enhance the antitumor effect of PD-1 inhibitor. Here, for the first time, we combined gastric artery chemoembolization with tislelizumab (a PD-1 inhibitor) for neoadjuvant therapy of a patient with LAGC. The patient achieved pCR after a D2 resection and tumor regression grade score was 1. After surgery, the patient received tislelizumab 200 mg per 3 weeks, and showed no sign of recurrence after 6 months of follow-up. The study indicated the use of tislelizumab and gastric artery chemoembolization for neoadjuvant therapy may bring a better pCR rate and prognosis of LAGC.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"101-105"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis. 基于单细胞测序分析构建巨噬细胞相关治疗效果预测因子的新方法

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-02-01 Epub Date: 2023-11-20 DOI: 10.1097/CJI.0000000000000497

Jianxiu Lin, Yang Ran, Tengfei Wu, Zishan Wang, Jinjin Zhao, Yun Tian

{"title":"A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.","authors":"Jianxiu Lin, Yang Ran, Tengfei Wu, Zishan Wang, Jinjin Zhao, Yun Tian","doi":"10.1097/CJI.0000000000000497","DOIUrl":"10.1097/CJI.0000000000000497","url":null,"abstract":"Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"33-48"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. 核心针活检作为三阴性乳腺癌过继细胞治疗的体外扩展TIL的替代来源。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-02-01 Epub Date: 2023-11-22 DOI: 10.1097/CJI.0000000000000495

Magdalena M Coman, Lajos Pusztai, Regina Hooley, Liva Andreveja, Leah Kim, Nikhil Joshi, Alexey Bersenev, Diane Krause, Tristen S Park

引用次数: 0

LOXL4 Shuttled by Tumor Cells-derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis. 肿瘤细胞来源的细胞外囊泡通过激活STAT1/PD-L1轴促进肝细胞癌的免疫逃逸

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1097/CJI.0000000000000496

Le Zhao, Ruifeng Pei, Yiren Ding, Zhan Su, Deqiang Li, Shuo Zhu, Lu Xu, Hongying Zhao, Wuyuan Zhou

{"title":"LOXL4 Shuttled by Tumor Cells-derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis.","authors":"Le Zhao, Ruifeng Pei, Yiren Ding, Zhan Su, Deqiang Li, Shuo Zhu, Lu Xu, Hongying Zhao, Wuyuan Zhou","doi":"10.1097/CJI.0000000000000496","DOIUrl":"10.1097/CJI.0000000000000496","url":null,"abstract":"Emerging evidence has validated that extracellular vesicles (EVs) regulate hepatocellular carcinoma (HCC) progression, while its role in HCC immune escape remains to be elucidated. This study investigates the role of EVs-encapsulated lysyl oxidase like-4 (LOXL4) derived from tumor cells in HCC immune escape. HCC-related microarray data sets GSE36376 and GSE87630 were obtained for differential analysis, followed by identifying the essential genes related to the prognosis of HCC patients. Bone marrow-derived macrophages were treated with EVs derived from mouse Hepa 1-6 cells and cocultured with CD8 + T cells to observe the CD8 + T-cell activity. At last, a mouse HCC orthotopic xenograft model was constructed to verify the effects of HCC cell-derived EVs on the immune escape of HCC cells and tumorigenicity in vivo by delivering LOXL4. It was found that ACAT1, C4BPA, EHHADH, and LOXL4 may be the essential genes related to the prognosis of HCC patients. On the basis of the TIMER database, there was a close correlation between LOXL4 and macrophage infiltration in HCC. Besides, STAT1 was closely related to LOXL4. In vitro experiments demonstrated that LOXL4 could induce programmed death-ligand 1 expression in macrophages and immunosuppression by activating STAT1. In vivo experiments also verified that HCC cell-derived EVs promoted the immune escape of HCC cells and tumorigenicity by delivering LOXL4. LOXL4 was delivered into macrophages via EVs to induce programmed death-ligand 1 by activating STAT1 and inhibiting the killing ability of CD8 + T cells to HCC cells, thus promoting immune escape in HCC.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"64-76"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation. 移植物中髓源性抑制细胞的比例是单倍体异基因造血干细胞移植中急性移植物抗宿主疾病的潜在预测指标。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2024-02-01 Epub Date: 2023-12-12 DOI: 10.1097/CJI.0000000000000499

Junjie Cao, Renzhi Pei, Ying Lu, Dong Chen, Xiaohong Du, Xuhui Liu, Shuangyue Li

{"title":"The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Junjie Cao, Renzhi Pei, Ying Lu, Dong Chen, Xiaohong Du, Xuhui Liu, Shuangyue Li","doi":"10.1097/CJI.0000000000000499","DOIUrl":"10.1097/CJI.0000000000000499","url":null,"abstract":"Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"54-63"},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effectiveness and Safety of Immune Checkpoint Inhibitors in Cancer Patients With Autoimmune Disease: A Retrospective Cohort Study. 癌症自身免疫性疾病患者免疫检查点抑制剂的有效性和安全性：回顾性队列研究。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2023-11-06 DOI: 10.1097/CJI.0000000000000492

Arjun A Raghavan, Sid Goutam, Grace Musto, Marc Geirnaert, Carrie Ye, Liam J O'Neil, Jeffrey Graham

{"title":"Effectiveness and Safety of Immune Checkpoint Inhibitors in Cancer Patients With Autoimmune Disease: A Retrospective Cohort Study.","authors":"Arjun A Raghavan, Sid Goutam, Grace Musto, Marc Geirnaert, Carrie Ye, Liam J O'Neil, Jeffrey Graham","doi":"10.1097/CJI.0000000000000492","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000492","url":null,"abstract":"Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, patients with pre-existing autoimmune diseases (PADs) have largely been excluded from clinical trials evaluating this drug class. This study evaluates the effectiveness and safety of ICI therapy in individuals with PAD in a real-world setting. A retrospective study of patients exposed to ICI therapy between 2012 and 2019 was conducted. Patients with PAD were identified and matched to an ICI-exposed group without PAD based on age, sex, and cancer type. Primary outcomes included toxicity, time to treatment failure, overall survival, and objective response rate. The association between PAD status and outcomes was determined using Cox and logistic regression modeling. A total of 813 patients exposed to ICI therapy were identified, of which 8.2% (N=67) had a PAD. When compared with a matched cohort without PAD (N=132), there was no significant difference in the rates of new immune-related adverse events (irAEs, 42.4% in the non-PAD group vs. 47.8% in the PAD group, P=0.474). After controlling for the type of ICI, there was no significant association between PAD status and irAE (odds ratio 1.67, 95% CI: 0.9-3.21 P=0.1). There was no significant association between overall survival and PAD status (hazard ratio 1.12, 95% CI: 0.76-1.66. P=0.56) or between time to treatment failure and PAD status (hazard ratio 0.82, 95% CI: 0.6-1.12, P=0.22). There was an association between PAD status and objective response rate (odds ratio 3.28, 95% CI: 1.28-8.38, P=0.013). In summary, PAD status was not associated with enhanced toxicity when compared with patients without PAD, with similar oncologic effectiveness between these 2 groups.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Concomitant Use of Proton Pump Inhibitors on Immunotherapy Clinical Response in Advanced Cancer Patients: Real-Life Setting. 同时使用质子泵抑制剂对晚期癌症患者免疫治疗临床反应的影响：现实生活环境。

IF 3.9 4区医学

Journal of Immunotherapy Pub Date : 2023-11-06 DOI: 10.1097/CJI.0000000000000494

Lorenzo Cantarelli, Fernando Gutiérrez Nicolás, Sara García Gil, Jose A Morales Barrios, Juana Oramas Rodriguez, Gloria J Nazco Casariego

{"title":"Effect of Concomitant Use of Proton Pump Inhibitors on Immunotherapy Clinical Response in Advanced Cancer Patients: Real-Life Setting.","authors":"Lorenzo Cantarelli, Fernando Gutiérrez Nicolás, Sara García Gil, Jose A Morales Barrios, Juana Oramas Rodriguez, Gloria J Nazco Casariego","doi":"10.1097/CJI.0000000000000494","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000494","url":null,"abstract":"The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38-2.59), P<0.001] and OS [HR: 2.02 (1.45-2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93-2.39), P=0.160] and OS [HR: 1.41 (0.81-2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49-1.70), P=0.791; HR: 1.10 (0.59-2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0