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JOURNAL ARTICLE
Ting Sun, Bin Liu, Lize Cai, Youxin Zhou, Wei Yang, Yanyan Li
PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs...
April 23, 2024: Journal of Neuro-oncology
#2
REVIEW
Guangxun Yuan, Mengke Ye, Yixi Zhang, Xun Zeng
Chimeric Antigen Receptor T cell (CAR-T) therapy has revolutionized cancer treatment, but its application to solid tumors is limited. CAR-T cells have poor incapability of entering, surviving, proliferating, and finally exerting function in the tumor microenvironment. This review summarizes the main strategies related to enhancing the infiltration, efficacy, antigen recognition, and production of CAR-T in solid tumors. Additional applications of CAR-γδ T and macrophages are also discussed. We believe CAR-T will be a milestone in treating solid tumors once these problems are solved...
April 23, 2024: Medical Oncology
#3
JOURNAL ARTICLE
Hiroaki Kanemura, Toshihide Yokoyama, Ryu Nakajima, Atsushi Nakamura, Hiroaki Kuroda, Yoshitaka Kitamura, Hiroyasu Shoda, Nobuaki Mamesaya, Yoshihiro Miyata, Tatsuro Okamoto, Kyoichi Okishio, Masahide Oki, Yuichi Sakairi, Toyofumi Fengshi Chen-Yoshikawa, Tadashi Aoki, Tatsuo Ohira, Isao Matsumoto, Kiyonobu Ueno, Takuro Miyazaki, Haruhisa Matsuguma, Hideoki Yokouchi, Tomoyuki Otani, Akihiko Ito, Kazuko Sakai, Yasutaka Chiba, Kazuto Nishio, Nobuyuki Yamamoto, Isamu Okamoto, Kazuhiko Nakagawa, Masayuki Takeda
INTRODUCTION: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. METHODS: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial...
April 2024: JTO clinical and research reports
#4
JOURNAL ARTICLE
Suyang Wang, Chao-Cheng Chen, Ming-Hung Hu, Michelle Cheng, Hsin-Fang Tu, Ya-Chea Tsai, Jr-Ming Yang, T C Wu, Chuan-Hsiang Huang, Chien-Fu Hung
BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7...
April 22, 2024: Journal of Translational Medicine
#5
JOURNAL ARTICLE
Andreas Roller, Iakov I Davydov, Petra C Schwalie, Martha L Serrano-Serrano, Astrid Heller, Nicolas Staedler, Cláudia S Ferreira, Gabriele Dietmann, Irina Klaman, Alberto Valdeolivas, Konstanty Korski, Michael A Cannarile
BACKGROUND: The immune status of a patient's tumor microenvironment (TME) may guide therapeutic interventions with cancer immunotherapy and help identify potential resistance mechanisms. Currently, patients' immune status is mostly classified based on CD8+tumor-infiltrating lymphocytes. An unmet need exists for comparable and reliable precision immunophenotyping tools that would facilitate clinical treatment-relevant decision-making and the understanding of how to overcome resistance mechanisms...
April 22, 2024: Journal for Immunotherapy of Cancer
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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)
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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