Xianmei Lv, Gaochen Lan, Qiusheng Guo
The correlation between triple-negative breast cancer (TNBC) and genes related to immunity and cancer stemness, particularly shared genes, remains unclear. This study aimed to investigate the correlation of immunity and cancer stemness with the molecular subtyping and survival rates in TNBC using bioinformatics approaches. Differential gene analysis was conducted to identify TNBC-associated differentially expressed genes (DEGs). Cancer stem cell (CSC)-related genes were obtained using weighted gene coexpression network analysis...
February 19, 2024: Journal of Immunotherapy
Haci Arak, Suna Erkiliç, Şendağ Yaslikaya, Eda Eylemer Mocan, Gökmen Aktaş, Melek Özdemir, Hüseyin Salih Semiz, Saadettin Kiliçkap, Faruk Özalp, Özlem Nuray Sever, Goncagül Akdağ, Ahmet Burak Ağaoğlu, Melike Özçelik, Murat Sari, Murat Arcagök, Hicran Anik, Şaziye Burçak Yayla, Nadiye Sever, Fatma Pinar Açar, İsmail Bayrakçi, Serdal Turhal, Murat Ayhan, Tülay Kuş
Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59...
February 7, 2024: Journal of Immunotherapy
Karlijn de Joode, Alfonso Rojas Mora, Ron H N van Schaik, Alfred Zippelius, Astrid van der Veldt, Camille Léa Gerard, Heinz Läubli, Olivier Michielin, Roger von Moos, Markus Joerger, Mitchell P Levesque, Stefanie Aeppli, Johanna Mangana, Cristina Mangas, Nadine Trost, Stefan Meyer, Sandra Leoni Parvex, Ron Mathijssen, Yannis Metaxas
Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene, an inhibitor of T-cell priming, are associated with auto and alloimmunity. Studies implied a role for these SNPs as surrogate markers for immunotherapy-outcome in patients with melanoma. However, no predictive SNPs are defined to date. We analyzed different CTLA-4 SNPs in a large multicenter cohort of patients with ipilimumab-treated melanoma and investigated possible correlations with treatment-related outcomes...
February 6, 2024: Journal of Immunotherapy
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
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...
February 1, 2024: Journal of Immunotherapy
Ye Sul Jeung, June Young Chun, Beom Kyu Choi, Seog Yun Park, Hyun-Ju Lim, Jong Woong Park, Ji-Youn Han, Youngjoo Lee
Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea...
January 29, 2024: Journal of Immunotherapy
Ru Zhou, Shu-Ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, Pinku Mukherjee
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...
January 25, 2024: Journal of Immunotherapy
Arman Zereshkian, Ruaa Shafi, Gregory R Pond, Sebastien J Hotte
The CheckMate-141 trial led to the approval of nivolumab in platinum-resistant metastatic/advanced squamous cell carcinomas of the head and neck (SCCHN). We evaluated the outcomes of SCCHN patients in Ontario, Canada, treated with nivolumab through retrospective review of the provincial treatment registry. Kaplan-Meier method was used to estimate overall survival (OS) and Cox regression to evaluate the prognostic effect of selected factors. Nivolumab was used as second-line therapy after disease relapse for curative-intent platinum chemotherapy (PC) (indication 1-I1), as second-line therapy post-PC in noncurative intent (indication 2-I2), and as first-line therapy in noncurative intent due to contraindication for PC (indication 3-I3)...
January 17, 2024: Journal of Immunotherapy
Katherine G Akers, Sabine Oskar, Bin Zhao, Andrew M Frederickson, Ashwini Arunachalam
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood...
December 19, 2023: Journal of Immunotherapy
Junjie Cao, Renzhi Pei, Ying Lu, Dong Chen, Xiaohong Du, Xuhui Liu, Shuangyue Li
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-/lowCD33+CD16-) by flow cytometry...
December 12, 2023: Journal of Immunotherapy
Le Zhao, Ruifeng Pei, Yiren Ding, Zhan Su, Deqiang Li, Shuo Zhu, Lu Xu, Hongying Zhao, Wuyuan Zhou
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...
December 4, 2023: Journal of Immunotherapy
Eric Olsen, Steven A Svoboda, Marjorie Montanez-Wiscovich, Sami K Saikaly
Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma...
November 27, 2023: Journal of Immunotherapy
Yufu Lin, Yabo Chen, Shenggan Lin, Jingmei Zheng, Xiuping Zhang, Lu Gan
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...
November 23, 2023: Journal of Immunotherapy
Magdalena M Coman, Lajos Pusztai, Regina Hooley, Liva Andreveja, Leah Kim, Nikhil Joshi, Alexey Bersenev, Diane Krause, Tristen S Park
Adoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TILs) have produced long-term response in metastatic cancers. TILs have traditionally been expanded from surgically resected specimens. Ultrasound-guided core needle biopsy (CNB) is an alternative method that avoids the morbidity of surgery and have added benefits which may include patients not amenable to surgery as well as the potential to produce TILs from multiple lesions in the same patient. We assessed the ability to produce and expand TILs from primary triple-negative breast cancer tumors from CNB (n=7) and demonstrate comparable expansion, phenotype and cytokine secretion after phorbol myristate acetate-ionomycin stimulation to TILs expanded from surgery (n=6)...
November 22, 2023: Journal of Immunotherapy
Jianxiu Lin, Yang Ran, Tengfei Wu, Zishan Wang, Jinjin Zhao, Yun Tian
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...
November 20, 2023: Journal of Immunotherapy
Lorenzo Cantarelli, Fernando Gutiérrez Nicolás, Sara García Gil, Jose A Morales Barrios, Juana Oramas Rodriguez, Gloria J Nazco Casariego
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...
November 6, 2023: Journal of Immunotherapy
Arjun A Raghavan, Sid Goutam, Grace Musto, Marc Geirnaert, Carrie Ye, Liam J O'Neil, Jeffrey Graham
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...
November 6, 2023: Journal of Immunotherapy
Ilit Turgeman, Anat Reiner Benaim, Stav Regev -Tsur, Shahar Turgeman, Mahmud Abu Amna, Omar Badran, Gil Bar-Sela
Metabolic pathways may regulate responses to cancer immunotherapy (IO). Due to its immunomodulatory properties, we sought to examine the association between serum vitamin B12 (VitB12) and survival in individuals with cancer treated with immune checkpoint inhibitors, compared with biological and chemotherapy. We collected data on patients with advanced cancer initiating intravenous antineoplastic treatment and a concomitant VitB12 measurement (elevated: >820 ng/L), between January 2010 and January 2022...
November 1, 2023: Journal of Immunotherapy
Vincent M D'Anniballe, Min-Nung Huang, Benjamin D Lueck, Lowell T Nicholson, Ian McFatridge, Michael D Gunn
Undifferentiated monocytes can be loaded with tumor antigens (Ag) and administered intravenously to induce antitumor cytotoxic T lymphocyte (CTL) responses. This vaccination strategy exploits an endogenous Ag cross-presentation pathway, where Ag-loaded monocytes (monocyte vaccines) transfer their Ag to resident splenic dendritic cells (DC), which then stimulate robust CD8 + CTL responses. In this study, we investigated whether monocyte vaccination in combination with CDX-301, a DC-expanding cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), could improve the antitumor efficacy of anti-programmed cell death (anti-PD-1) immune checkpoint blockade...
November 2023: Journal of Immunotherapy
Ji Lin, Paola Rodriguez-Martinez, Thein Hlaing Oo, Shuyu E, Jeffrey Jorgensen, Cristhiam M Rojas-Hernandez
Immune checkpoint inhibitors (ICI) have gained approval as a treatment for a wide array of cancers. Their mechanism of action prevents the inactivation of cytotoxic T-cells, allowing for its cytotoxic response. However, the upregulation of the immune system by ICI also leads to many undesired adverse events known as immune-related adverse events (irAEs), ranging from dermatologic manifestations, such as rashes, to inflammation of mucous membranes, to hematologic toxicities. Here, we report a case of ICI-induced pure white cell aplasia, secondary to the agent durvalumab, which responded to treatment with filgrastim, prednisone, and cyclosporine...
October 30, 2023: Journal of Immunotherapy
Chantal Decroisette, Laurent Greillier, Hubert Curcio, Maurice Pérol, Charles Ricordel, Jean-Bernard Auliac, Lionel Falchero, Remi Veillon, Sabine Vieillot, Florian Guisier, Marie Marcq, Grégoire Justeau, Laurence Bigay-Game, Marie Bernardi, Hélène Doubre, Julian Pinsolle, Karim Amrane, Christos Chouaïd, Renaud Descourt
Outside clinical trials, few data are available on the effect of long-term first-line pembrolizumab in patients with advanced non-small-cell lung cancers with ≥50% of tumor cells expressing programmed cell death ligand 1 (PD-L1). This French, multicenter study included consecutive advanced patients with non-small-cell lung cancer given first-line pembrolizumab alone between May 2017 (authorization date for this indication) and November 2019 (authorization date for pembrolizumab-chemotherapy combination)...
October 9, 2023: Journal of Immunotherapy
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