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JOURNAL ARTICLE
Wei Zhu, Zhiming Zhang, Jinzhang Chen, Xiaolan Chen, Lei Huang, Xiaoyong Zhang, Xuan Huang, Na Ma, Weikang Xu, Xuan Yi, Xinyu Lu, Xin Fu, Siwei Li, Guoheng Mo, Yiyue Wang, Guosheng Yuan, Mengya Zang, Qi Li, Xiaotao Jiang, Yajing He, Sha Wu, Yukai He, Yongyin Li, Jinlin Hou
Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc ) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo...
April 20, 2024: Signal Transduction and Targeted Therapy
#2
REVIEW
Yuke Wang, Yan Zeng, Wenyong Yang, Xiuxuan Wang, Jingwen Jiang
BACKGROUND: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential...
April 8, 2024: Phytomedicine
#3
JOURNAL ARTICLE
Mark S Lee, Peter J Tuohy, Caleb Y Kim, Philip P Yost, Katrina Lichauco, Heather L Parrish, Koenraad Van Doorslaer, Michael S Kuhns
CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al...
April 19, 2024: ELife
#4
REVIEW
Mariusz A Wasik, Patricia M Kim, Reza Nejati
While normal B- and T-lymphocytes require antigenic ligands to become activated via their B- and T-cell receptors (BCR and TCR, respectively), B- and T-cell lymphomas show the broad spectrum of cell activation mechanisms regarding their dependence on BCR or TCR signaling, including loss of such dependence. These mechanisms are generally better understood and characterized for B-cell than for T-cell lymphomas. While some lymphomas, particularly the indolent, low-grade ones remain antigen-driven, other retain dependence on activation of their antigen receptors seemingly in an antigen-independent manner with activating mutations of the receptors playing a role...
2024: Frontiers in Oncology
#5
JOURNAL ARTICLE
Bo Cheng, Caichen Li, Jianfu Li, Longlong Gong, Peng Liang, Ying Chen, Shuting Zhan, Shan Xiong, Ran Zhong, Hengrui Liang, Yi Feng, Runchen Wang, Haixuan Wang, Hongbo Zheng, Jun Liu, Chengzhi Zhou, Wenlong Shao, Yuan Qiu, Jiancong Sun, Zhanhong Xie, Zhu Liang, Chenglin Yang, Xiuyu Cai, Chunxia Su, Wei Wang, Jianxing He, Wenhua Liang
Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon's optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs...
April 19, 2024: Signal Transduction and Targeted Therapy
#6
JOURNAL ARTICLE
Yuto Naoi, Takao Morinaga, Joji Nagasaki, Ryo Ariyasu, Youki Ueda, Kazuo Yamashita, Wenhao Zhou, Shusuke Kawashima, Katsushige Kawase, Akiko Honobe-Tabuchi, Takehiro Ohnuma, Tatsuyoshi Kawamura, Yoshiyasu Umeda, Yu Kawahara, Yasuhiro Nakamura, Yukiko Kiniwa, Osamu Yamasaki, Satoshi Fukushima, Masahito Kawazu, Yutaka Suzuki, Hiroyoshi Nishikawa, Toyoyuki Hanazawa, Mizuo Ando, Takashi Inozume, Yosuke Togashi
T cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed anti-tumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to PD-1 blockade...
April 18, 2024: Cancer Research
#7
JOURNAL ARTICLE
Anastasia V Pavlova, Ivan V Zvyagin, Mikhail Shugay
An individual's T-cell repertoire constantly changes under the influence of external and internal factors. Cells that do not receive a stimulatory signal die, while those that encounter and recognize a pathogen or receive a co-stimulatory signal divide, resulting in clonal expansions. T-cell clones can be traced by monitoring the presence of their unique T-cell receptor (TCR) sequence, which is assembled de novo through a process known as V(D)J rearrangement. Tracking T cells can provide valuable insights into the survival of cells after hematopoietic stem cell transplantation (HSCT) or cancer treatment response and can indicate the induction of protective immunity by vaccination...
2024: Frontiers in Immunology
#8
JOURNAL ARTICLE
Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W Zimmerman, Thomas Eder, Diaaeldin I Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Daniel Pölöske, Emina Hubanic, Dennis Jungherz, Tony Andreas Müller, Myint Myat Khine Aung, Anna Orlova, Ha Thi Thanh Pham, Kerstin Zimmel, Thomas Krausgruber, Christoph Bock, Mathias Müller, Maik Dahlhoff, Auke Boersma, Thomas Rülicke, Roman Fleck, Elvin Dominic de Araujo, Patrick Thomas Gunning, Tero Aittokallio, Satu Mustjoki, Takaomi Sanda, Sylvia Hartmann, Florian Grebien, Gregor Hoermann, Torsten Haferlach, Philipp Bernhard Staber, Heidi Anne Neubauer, Alfred Thomas Look, Marco Herling, Richard Moriggl
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR...
April 15, 2024: Journal of Clinical Investigation
#9
REVIEW
Ying Jin, Haiyi Wu, Jianzhao Liu, William C Cho, Guoqi Song
BACKGROUND AND OBJECTIVE: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) gene editing and CRISPR/Cas9 screening libraries are hot topics, and have high application values in the diagnosis and treatment of genetic diseases, and the improvement of prognosis. The major treatment of B-cell lymphoma is chemotherapy combined with biological therapy. Due to the individual specificity and the emergence of drug resistance, the therapeutic efficacy varies...
March 31, 2024: Translational Cancer Research
#10
JOURNAL ARTICLE
Xiao Liu, Qianqian Cui, Nan Qin
BACKGROUND: KLRB1 is downregulated in various cancer types. Nevertheless, the specific involvement of KLRB1 in the context of breast cancer (BRCA) has not been fully elucidated. This research aimed to explore its clinical value in BRCA. METHODS: A dataset comprising 1,109 BRCA samples and 113 healthy samples was retrieved from The Cancer Genome Atlas (TCGA) database to establish the association between KLRB1 expression and pan-cancer. Subsequently, an analysis was executed to explore the link between KLRB1 and BRCA...
March 31, 2024: Translational Cancer Research
#11
JOURNAL ARTICLE
Lufei Ren, Yuyang Li, Yifan Feng, Zhe Zhang, Huijun Yang, Min Li
BACKGROUND: Chloride channel-3 ( CLCN3 ), a crucial component of the voltage-gated chloride channel family, is implicated in numerous physiological and pathophysiological processes. This study aimed to investigate the characteristics of CLCN3 in pancancer and its influence on the immune response through the use of a range of databases. Concurrently, we assessed the impact of CLCN3 on the proliferation of ovarian cancer (OC) cells and explored its potential mechanisms. METHODS: We employed the Tumor Immune Estimation Resource (TIMER) 2...
March 31, 2024: Translational Cancer Research
#12
JOURNAL ARTICLE
Construction and validation of a prognostic model for stemness-related genes in lung adenocarcinoma.
Hong Zhang, Chenlin Cao, Hua Xiong
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with poor overall prognosis. Early identification of high-risk patients and individualized treatment can help extend the survival time of patients. This study aimed to construct and validate a prognostic prediction least absolute shrinkage and selection operator (LASSO) model for stemness-related genes in LUAD. METHODS: Firstly, LUAD RNA-sequencing data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database...
March 31, 2024: Translational Cancer Research
#13
JOURNAL ARTICLE
Jing-Ying Li, Chen-Ji Hu, Hui Peng, En-Qiang Chen
BACKGROUND: Breast cancer (BC) is the most prevalent cancer type and is the principal cause of cancer-related death in women. Anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immunotherapy has shown promising effects in metastatic triple-negative breast cancer (TNBC), but the potential factors affecting its efficacy have not been elucidated. Immune-related long noncoding RNAs (irlncRNAs) have been reported to be involved in immune escape to influence the carcinogenic process through the PD-1/PD-L1 signaling pathway...
March 31, 2024: Translational Cancer Research
#14
Russell W Cochrane, Rob A Robino, Bryan Granger, Eva Allen, Silvia Vaena, Martin J Romeo, Aguirre A de Cubas, Stefano Berto, Leonardo M R Ferreira
Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T-cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28 activated Tregs...
April 1, 2024: bioRxiv
#15
Kiera B Wilhelm, Anand Vissa, Jay T Groves
UNLABELLED: Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells. While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell signal integration mechanisms that rely on monovalent, membrane-associated, and relatively weakly-binding ligand in the context of cellular adhesion. Commonly used antibodies and their derivatives bind much more strongly than native peptide-MHC (pMHC) ligands bind their cognate TCRs. Because ligand dwell time is a critical parameter that tightly correlates with physiological function of the TCR signaling system, there is a general need, both in research and therapeutics, for universal TCR ligands with controlled kinetic binding parameters...
April 2, 2024: bioRxiv
#16
JOURNAL ARTICLE
Ling Wang, Zhaoduan Liang, Yunzhuo Guo, Jean de Dieu Habimana, Yuefei Ren, Obed Boadi Amissah, Omar Mukama, Siqi Peng, Xuanyan Ding, Linshuang Lv, Junyi Li, Min Chen, Zhaoming Liu, Rongqi Huang, Yinchao Zhang, Yi Li, Zhiyuan Li, Yirong Sun
Antigen-specific T cell receptor-engineered T cell (TCR-T) based immunotherapy has proven to be an effective method to combat cancer. In recent years, cross-talk between the innate and adaptive immune systems may be requisite to optimize sustained antigen-specific immunity, and the stimulator of interferon genes (STING) is a promising therapeutic target for cancer immunotherapy. The level of expression or presentation of antigen in tumor cells affects the recognition and killing of tumor cells by TCR-T. This study aimed at investigating the potential of innate immune stimulation of T cells and engineered T cells to enhance immunotherapy for low-expression antigen cancer cells...
April 13, 2024: Cell Death & Disease
#17
REVIEW
Fernando Alvarez, Zhiyang Liu, Alexandre Bay, Ciriaco A Piccirillo
Foxp3+ TREG cells have been at the focus of intense investigation for their recognized roles in preventing autoimmunity, facilitating tissue recuperation following injury, and orchestrating a tolerance to innocuous non-self-antigens. To perform these critical tasks, TREG cells undergo deep epigenetic, transcriptional, and post-transcriptional changes that allow them to adapt to conditions found in tissues both at steady-state and during inflammation. The path leading TREG cells to express these tissue-specialized phenotypes begins during thymic development, and is further driven by epigenetic and transcriptional modifications following TCR engagement and polarizing signals in the periphery...
2024: Frontiers in Immunology
#18
JOURNAL ARTICLE
Karin Teppert, Isabella Elias Yonezawa Ogusuku, Caroline Brandes, Vera Herbel, Nora Winter, Niels Werchau, Svetlana Khorkova, Christian Wöhle, Nojan Jelveh, Kevin Bisdorf, Boris Engels, Thomas Schaser, Kathleen Anders, Annette Künkele, Dominik Lock
Acute myeloid leukemia (AML), a fast-progressing hematological malignancy affecting myeloid cells, is typically treated with chemotherapy or hematopoietic stem cell transplantation. However, approximately half of the patients face relapses and 5-year survival rates are poor. With the goal to facilitate dual-specificity, boosting anti-tumor activity, and minimizing the risk for antigen escape, this study focused on combining chimeric antigen receptor (CAR) and T cell receptor (TCR) technologies. CAR'TCR-T cells, co-expressing a CD33-CAR and a transgenic dNPM1-TCR, revealed increased and prolonged anti-tumor activity in vitro , particularly in case of low target antigen expression...
June 20, 2024: Mol Ther Oncol
#19
JOURNAL ARTICLE
Martin Lauss, Bengt Phung, Troels Holz Borch, Katja Harbst, Kamila Kaminska, Anna Ebbesson, Ingrid Hedenfalk, Joan Yuan, Kari Nielsen, Christian Ingvar, Ana Carneiro, Karolin Isaksson, Kristian Pietras, Inge Marie Svane, Marco Donia, Göran Jönsson
Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways are observed in approximately 25% of ICB resistant cases...
April 9, 2024: Nature Communications
#20
JOURNAL ARTICLE
Tatyana O Nakonechnaya, Bruno Moltedo, Ekaterina V Putintseva, Sofya Leyn, Dmitry A Bolotin, Olga V Britanova, Mikhail Shugay, Dmitriy M Chudakov
Suppressive function of regulatory T cells (Treg) is dependent on signaling of their antigen receptors triggered by cognate self, dietary, or microbial peptides presented on MHC II. However, it remains largely unknown whether distinct or shared repertoires of Treg TCRs are mobilized in response to different challenges in the same tissue or the same challenge in different tissues. Here we use a fixed TCRβ chain FoxP3-GFP mouse model to analyze conventional (eCD4) and regulatory (eTreg) effector TCRα repertoires in response to six distinct antigenic challenges to the lung and skin...
April 9, 2024: ELife
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