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JOURNAL ARTICLE
Luca Bertola, Benedetta Pellizzoni, Chiara Giudice, Valeria Grieco, Roberta Ferrari, Lavinia E Chiti, Damiano Stefanello, Martina Manfredi, Donatella De Zani, Camilla Recordati
Cutaneous and subcutaneous mast cell tumors (MCTs) are common canine neoplasms characterized by variable biological behavior. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) can be effective prognostic markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine MCTs and their relationship with histological location (cutaneous, subcutaneous) and histologic nodal metastatic status (HN0-3). Thirty-eight MCTs (26 cutaneous, 12 subcutaneous) from 33 dogs with known sentinel lymph node (SLN) metastatic status were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells)...
April 22, 2024: Veterinary Pathology
#2
Shadi Zahedi, Kent Riemondy, Andrea M Griesinger, Andrew M Donson, Rui Fu, Michele Crespo, John DeSisto, Madeline M Groat, Emil Bratbak, Adam Green, Todd C Hankinson, Michael Handler, Rajeev Vibhakar, Nicholas Willard, Nicholas K Foreman, Jean Mulcahy Levy
UNLABELLED: Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies. We utilized single cell RNA sequencing (scRNA-seq), spatial transcriptomics, and cytokine analyses to characterize and understand tumor and immune cell heterogeneity across pLGG. scRNA-seq revealed tumor and immune cells within the tumor microenvironment (TME)...
April 10, 2024: bioRxiv
#3
Andras Heczey, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy Courtney, Azlann Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John Maris, Dan Martinez, Jennier Pogoriler, Navin Varadarajan, Sachin Thakkar, Deborah Lyon, Natasha Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos Ramos, Premal Lulla, Tannaz Armaghany, Bambi Grilley, Gianpietro Dotti, Leonid Metelitsa, Helen Heslop, Malcolm Brenner, Pavel Sumazin
Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks...
April 3, 2024: Research Square
#4
JOURNAL ARTICLE
Ottavia De Simoni, Melania Scarpa, Ignazio Castagliuolo, Astghik Stepanyan, Imerio Angriman, Andromachi Kotsafti, Camilla Nacci, Federico Scognamiglio, Silvia Negro, Antonella D'Angelo, Valentina Chiminazzo, Gianluca Businello, Cesare Ruffolo, Roberta Salmaso, Boris Franzato, Mario Gruppo, Pierluigi Pilati, Antonio Scapinello, Anna Pozza, Tommaso Stecca, Marco Massani, Ivana Cataldo, Stefano Brignola, Angelo Paolo Dei Tos, Carlotta Ceccon, Vincenza Guzzardo, Chiara Vignotto, Luca Facci, Isacco Maretto, Marco Agostini, Francesco Marchegiani, Giulia Becherucci, Maurizio Zizzo, Giovanni Bordignon, Roberto Merenda, Giovanni Pirozzolo, Alfonso Recordare, Giulia Pozza, Mario Godina, Isabella Mondi, Daunia Verdi, Corrado Da Lio, Licia Laurino, Luca Saadeh, Giorgio Rivella, Silvio Guerriero, Chiara Romiti, Giuseppe Portale, Chiara Cipollari, Ylenia Camilla Spolverato, Giulia Noaro, Roberto Cola, Salvatore Candioli, Laura Gavagna, Fabio Ricagna, Monica Ortenzi, Mario Guerrieri, Giovanni Tagliente, Monica Tomassi, Umberto Tedeschi, Beatrice Salmaso, Gianluca Buzzi, Dario Parini, Daniela Prando, Matteo Zuin, Francesca Bergamo, Vittorina Zagonel, Andrea Porzionato, Francesco Cavallin, Barbara Di Camillo, Loretta Di Cristoforo, Quoc Riccardo Bao, Salvatore Pucciarelli, Romeo Bardini, Gaya Spolverato, Matteo Fassan, Marco Scarpa
BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583)...
April 22, 2024: Cancer
#5
JOURNAL ARTICLE
V P Snijesh, Vidya P Nimbalkar, Sharada Patil, Savitha Rajarajan, C E Anupama, S Mahalakshmi, Annie Alexander, Ramu Soundharya, Rakesh Ramesh, B S Srinath, Mohit Kumar Jolly, Jyothi S Prabhu
BACKGROUND: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. METHODS: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline...
April 20, 2024: Translational Oncology
#6
JOURNAL ARTICLE
Huanhuan Xie, Wenjing Liu, Mi Yang
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors, and stages III and IV are frequently diagnosed. In recent years, immunotherapy has achieved remarkable results in recurrent/metastatic NPC, and many studies related to immunotherapy for NPC have been published. However, to date, no relevant bibliometric studies have been published. The trends and research focus on NPC immunotherapy are analyzed in this study through bibliometric analysis, which is conducive to better understanding the status quo and future trends of immunotherapy for NPC...
April 19, 2024: Medicine (Baltimore)
#7
JOURNAL ARTICLE
Qiang Lou, Ming-Wei Zhan, Yu-Qi Lai, Xu-Xin Zhan, Xue-Jun Shang
OBJECTIVE: To investigate the therapeutic mechanism of oxalis decoction on CNP rats by regulating cGAS-STING signaling pathway. METHODS: Thirty specific pathogen-free SD male rats were randomly divided into normal control group (NC), model control group (MC), and oxalis decoction group (OD),with 10 rats in each group.The left and right anterior abdominal lobes of each group were surgically exposed.The normal control group was injected by the same volume of normal saline...
December 2023: Zhonghua Nan Ke Xue, National Journal of Andrology
#8
JOURNAL ARTICLE
Na Li, Jiangli Shen, Ximin Qiao, Qiang Liu, Xiaoqiang Dai, Xiongwen Jiao
CONTEXT: Procollagen C-endopeptidase enhancer 2 (PCOLCE2) is associated with the degradation of the extracellular matrix and collagen-chain trimerization, playing a yet unexplored role in tumor prognosis. OBJECTIVE: The study intended to characterize PCOLCE2's influence on colorectal cancer (CRC) using expression analysis and to investigate its prognostic potential. DESIGN: The research team performed a genetic analysis using genetic databases, including The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), the Tumor IMmune Estimation Resource (TIMER), and LinkedOmics...
April 18, 2024: Alternative Therapies in Health and Medicine
#9
JOURNAL ARTICLE
Marco Cozzolino, Gyorgy Panyi
BACKGROUND: The unique microenvironment in tumors inhibits the normal functioning of tumor-infiltrating lymphocytes, leading to immune evasion and cancer progression. Over-activation of KCa3.1 using positive modulators has been proposed to rescue the anti-tumor response. One of the key characteristics of the tumor microenvironment is extracellular acidity. Herein, we analyzed how intra- and extracellular pH affects K+ currents through KCa3.1 and if the potency of two of its positive modulators, Riluzole and SKA-31, is pH sensitive...
2024: Frontiers in Pharmacology
#10
JOURNAL ARTICLE
Tomáš Blažek, Marek Petráš, Pavel Hurník, Petr Matoušek, Lukáš Knybel, Zuzana Zděblová Čermáková, Jan Štembírek, Jakub Cvek, Renata Soumarová
INTRODUCTION: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment. METHODS: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023...
2024: Frontiers in Oncology
#11
JOURNAL ARTICLE
Xiaofen Li, Nan Zhou, Yu Yang, Zijian Lu, Hongfeng Gou
Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second-line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second-line nab-paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first-line chemotherapy were enrolled. Subjects received nab-paclitaxel 125 mg/m2 on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR)...
April 18, 2024: Cancer Science
#12
JOURNAL ARTICLE
Da-Feng Lin, Hai-Lin Li, Ting Liu, Xiao-Fei Lv, Chuan-Miao Xie, Xiao-Min Ou, Jian Guan, Ye Zhang, Wen-Bin Yan, Mei-Lin He, Meng-Yuan Mao, Xun Zhao, Lian-Zhen Zhong, Wen-Hui Chen, Qiu-Yan Chen, Hai-Qiang Mai, Rou-Jun Peng, Jie Tian, Lin-Quan Tang, Di Dong
BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts...
April 19, 2024: Journal of the National Cancer Institute
#13
JOURNAL ARTICLE
M C Liefaard, A van der Voort, M van Seijen, B Thijssen, J Sanders, S Vonk, L Mittempergher, R Bhaskaran, L de Munck, A E van Leeuwen-Stok, R Salgado, H M Horlings, E H Lips, G S Sonke
Tumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial...
April 18, 2024: NPJ Breast Cancer
#14
JOURNAL ARTICLE
Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells.
Dana Piovesan, Amber E de Groot, Soonweng Cho, Amy E Anderson, Rebecca D Ray, Amita Patnaik, Paul G Foster, Casey G Mitchell, Alejandra Y Lopez Espinoza, Wandi S Zhu, Carlo E Stagnaro, Hema Singh, Xiaoning Zhao, Lisa Seitz, Nigel P Walker, Matthew J Walters, Kelsey E Sivick
TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding...
April 18, 2024: Cancer Research
#15
JOURNAL ARTICLE
Aida Jlassi, Rim Rejaibi, Maroua Manai, Ghada Sahraoui, Fatma Zahra Guerfali, Lamia Charfi, Amel Mezlini, Mohamed Manai, Karima Mrad, Raoudha Doghri
INTRODUCTION: Immunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer...
2024: Frontiers in Oncology
#16
JOURNAL ARTICLE
Is Programmed Death-Ligand 1 of Prognostic Significance in Triple-Negative Female Mammary Carcinoma?
Amal Mostafa Sanad, Wael Shawky Ibrahim, Iman Mohamed Ezzo, Rania Mohamed Sabry
INTRODUCTION: The most widespread female malignancy is breast cancer (BC), considerable percentage of patients with triple-negative BC (TNBC) experience rapid progression, recurrence, and metastasis. BC has not historically been treated as an immunogenic cancer. Nonetheless, several researchers have started to concentrate on immunotherapy. AIM: The aim of the study is to investigate the immunohistochemical (IHC) expression of programmed death-ligand 1 (PD-L1) by stromal tumor-infiltrating lymphocytes (TILs) and tumor cells (TC) in female (TNBC) and to correlate with pathological features of such tumors, particularly those determine biologic behavior, such as the grade and stage the overall survival...
2024: Journal of Microscopy and Ultrastructure
#17
JOURNAL ARTICLE
Celia Gomar, Claudia Augusta Di Trani, Angela Bella, Leire Arrizabalaga, Jose Gonzalez-Gomariz, Myriam Fernandez-Sendin, Maite Alvarez, Joan Salvador Russo-Cabrera, Nuria Ardaiz, Fernando Aranda, Timo Schippers, Marisol Quintero, Ignacio Melero, Klaus K Orlinger, Henning Lauterbach, Pedro Berraondo
BACKGROUND: Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes. Combination strategies to maximize the antitumor effectiveness of LCMV-based immunotherapies are being explored...
April 16, 2024: Journal for Immunotherapy of Cancer
#18
JOURNAL ARTICLE
Josipa Raguz, Catarina Pinto, Theresa Pölzlbauer, Mohamed Habbeddine, Sandra Rosskopf, Judith Strauß, Valentin Just, Sarah Schmidt, Katell Bidet Huang, Felix Stemeseder, Timo Schippers, Ethan Stewart, Jakub Jez, Pedro Berraondo, Klaus K Orlinger, Henning Lauterbach
BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells...
April 17, 2024: Journal for Immunotherapy of Cancer
#19
JOURNAL ARTICLE
David König, Michael Sandholzer, Sarp Uzun, Andreas Zingg, Reto Ritschard, Helen Thut, Katharina Glatz, Elisabeth A Kappos, Dirk J Schaefer, Christoph Kettelhack, Jakob R Passweg, Andreas Holbro, Katharina Baur, Michael Medinger, Andreas Buser, Didier Lardinois, Lukas T Jeker, Nina Khanna, Frank Stenner, Benjamin Kasenda, Krisztian Homicsko, Matthias Matter, Natalia Rodrigues Mantuano, Alfred Zippelius, Heinz Läubli
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To our knowledge, this is the first case of clonal selection of a pre-existing non-dominant tumor cell clone and it demonstrates a mechanism involved in secondary resistance to TIL-ACT that could potentially change current clinical practice, because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before the treatment with TIL-ACT...
April 17, 2024: Cancer Immunology Research
#20
JOURNAL ARTICLE
Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B Villafania, Jennifer L Sauter, Michael Offin, Marjorie G Zauderer, Marc Ladanyi
PURPOSE: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using the FACETS algorithm. RESULTS: 210 patients were evaluable for LOH analysis using FACETS...
April 17, 2024: Clinical Cancer Research
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