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JOURNAL ARTICLE
Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang
PURPOSE: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors (ICIs), presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential. MATERIALS AND METHODS: We explored the molecular characteristics of CD8+ T cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis...
April 12, 2024: Cancer Research and Treatment: Official Journal of Korean Cancer Association
#22
REVIEW
Sota Kurihara, Akihiro Ishikawa, Shin Kaneko
In recent years, immunotherapy has become a standard cancer therapy, joining surgery, chemotherapy, and radiation therapy. This therapeutic approach involves the use of patient-derived antigen-specific T cells or genetically modified T cells engineered with chimeric antigen receptors (CAR) or T cell receptors (TCR) that specifically target cancer antigens. However, T cells require ex vivo stimulation for proliferation when used in therapy, and the resulting "exhaustion," which is characterized by a diminished proliferation capacity and anti-tumor activity, poses a significant challenge...
April 18, 2024: Inflammation and Regeneration
#23
JOURNAL ARTICLE
Xiyue Xu, Yidan Zhang, Yaxiao Lu, Xiaoyan Zhang, Cuicui Zhao, Jiesong Wang, Qingpei Guan, Yingfang Feng, Meng Gao, Jingwei Yu, Zheng Song, Xia Liu, Zahra Golchehre, Lanfang Li, Weicheng Ren, Qiang Pan-Hammarström, Huilai Zhang, Xianhuo Wang
Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL...
April 18, 2024: Cancer Research
#24
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
#25
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
#26
JOURNAL ARTICLE
Ayten Kayı Cangır, Süleyman Gökalp Güneş, Kaan Orhan, Hilal Özakıncı, Yusuf Kahya, Duru Karasoy, Serpil Dizbay Sak
BACKGROUND: Non-small cell lung cancer (NSCLC) patients without lymph node (LN) metastases (pN0) may exhibit different survival rates, even when their T stage is similar. This divergence could be attributed to the current pathology practice, wherein LNs are examined solely in two-dimensional (2D). Unfortunately, adhering to the protocols of 2D pathological examination does not ensure the exhaustive sampling of all excised LNs, thereby leaving room for undetected metastatic foci in the unexplored depths of tissues...
December 2024: Journal of Pathology Informatics
#27
JOURNAL ARTICLE
Thea Sjøgren, Shahinul Islam, Igor Filippov, Adrianna Jebrzycka, André Sulen, Lars E Breivik, Alexander Hellesen, Anders P Jørgensen, Kari Lima, Liina Tserel, Kai Kisand, Pärt Peterson, Annamari Ranki, Eystein S Husebye, Bergithe E Oftedal, Anette S B Wolff
Immune tolerance fails in autoimmune polyendocrine syndrome type 1 (APS-1) because of AIRE mutations. We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from in vitro expanded Tregs in APS-1 patients compared to healthy controls. We revealed only CD52 and LTB (down) and TXNIP (up) as consistently differentially expressed genes in the datasets. There were furthermore no large differences of the TCR-repertoire of expanded Tregs between the cohorts, but unique patients showed a more restricted use of specific clonotypes...
April 19, 2024: IScience
#28
JOURNAL ARTICLE
Kun Zheng, Youlong Hai, Hongqi Chen, Yukun Zhang, Xiaoyong Hu, Kai Ni
BACKGROUND: Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC). METHODS: Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns...
April 17, 2024: Journal of Translational Medicine
#29
JOURNAL ARTICLE
Alexandra Flemming
No abstract text is available yet for this article.
April 17, 2024: Nature Reviews. Immunology
#30
JOURNAL ARTICLE
Chansavath Phetsouphanh, Brendan Jacka, Sara Ballouz, Katherine J L Jackson, Daniel B Wilson, Bikash Manandhar, Vera Klemm, Hyon-Xhi Tan, Adam Wheatley, Anupriya Aggarwal, Anouschka Akerman, Vanessa Milogiannakis, Mitchell Starr, Phillip Cunningham, Stuart G Turville, Stephen J Kent, Anthony Byrne, Bruce J Brew, David R Darley, Gregory J Dore, Anthony D Kelleher, Gail V Matthews
This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months...
April 17, 2024: Nature Communications
#31
JOURNAL ARTICLE
Wei Liu, Hesong Zou, Lianting Chen, Wenyang Huang, Rui Lv, Yan Xu, Huimin Liu, Yin Shi, Kefei Wang, Yi Wang, Wenjie Xiong, Shuhui Deng, Shuhua Yi, Weiwei Sui, Guangxin Peng, Yueshen Ma, Huijun Wang, Lulu Lv, Jianxiang Wang, Jun Wei, Lugui Qiu, Wenting Zheng, Dehui Zou
BACKGROUND: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL...
April 16, 2024: Journal for Immunotherapy of Cancer
#32
JOURNAL ARTICLE
Zhi Hu, Meiling Zheng, Ziyu Guo, Wenhui Zhou, Wenyu Zhou, Nan Yao, Guiying Zhang, Qianjin Lu, Ming Zhao
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions...
April 15, 2024: Clinical Immunology: the Official Journal of the Clinical Immunology Society
#33
JOURNAL ARTICLE
Qizhi Fan, Yiyan Wang, Jun Cheng, Boyu Pan, Xiaofang Zang, Renfeng Liu, Youwen Deng
BACKGROUND: T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear. METHODS: In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion...
2024: Frontiers in Immunology
#34
REVIEW
Esimebia Adjovi Amegashie, Prince Asamoah, Lawrencia Emefa Ami Ativi, Mildred Adusei-Poku, Evelyn Yayra Bonney, Emmanuel Ayitey Tagoe, Elijah Paintsil, Kwasi Torpey, Osbourne Quaye
People living with HIV (PLWH) usually suffer from co-infections and co-morbidities including respiratory tract infections. SARS-CoV-2 has been reported to cause respiratory infections. There are uncertainties in the disease severity and immunological response among PLWH who are co-infected with COVID-19. This review outlines the current knowledge on the clinical outcomes and immunological response to SARS-CoV-2 among PLWH. Literature was searched in Google scholar, Scopus, PubMed, and Science Direct conforming with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines from studies published from January 2020 to June 2023...
2024: Experimental Biology and Medicine
#35
JOURNAL ARTICLE
Darryl Kato, Regina Wai-Yan Choy, Eda Canales, Ryan A Dick, April D Lake, Nathan D Shapiro, Elbert Chin, Jiayao Li, Jennifer R Zhang, Qiaoyin Wu, Roland D Saito, Sammy Metobo, Evangelos Aktoudianakis, Scott D Schroeder, Zheng-Yu Yang, Dylan M Glatt, Scott Balsitis, Lindsay Gamelin, Mei Yu, Guofeng Cheng, William E Delaney, John O Link
Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure. A series of dihydropyridoisoquinolizinone (DHQ) inhibitors of human poly(A) polymerases PAPD5/7 were reported to suppress HBsAg in vitro...
April 11, 2024: ACS Medicinal Chemistry Letters
#36
JOURNAL ARTICLE
Yan Zhao, Yangyang Yu, Xiangmin Li, Ayao Guo
BACKGROUND: Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). METHODS: PTX resistance-related genes were screened by bioinformatics. CEBPD and VAMP3 expression in clinical TNBC samples was examined by immunohistochemistry...
April 16, 2024: Journal of Experimental & Clinical Cancer Research: CR
#37
JOURNAL ARTICLE
Joline Ingels, Laurenz De Cock, Dieter Stevens, Rupert L Mayer, Fabien Théry, Guillem Sanchez Sanchez, David Vermijlen, Karin Weening, Saskia De Smet, Nele Lootens, Marieke Brusseel, Tasja Verstraete, Jolien Buyle, Eva Van Houtte, Pam Devreker, Kelly Heyns, Stijn De Munter, Sandra Van Lint, Glenn Goetgeluk, Sarah Bonte, Lore Billiet, Melissa Pille, Hanne Jansen, Eva Pascal, Lucas Deseins, Lies Vantomme, Maarten Verdonckt, Ria Roelandt, Thomas Eekhout, Niels Vandamme, Georges Leclercq, Tom Taghon, Tessa Kerre, Floris Vanommeslaeghe, Annemieke Dhondt, Liesbeth Ferdinande, Jo Van Dorpe, Liesbeth Desender, Frederic De Ryck, Frank Vermassen, Veerle Surmont, Francis Impens, Björn Menten, Karim Vermaelen, Bart Vandekerckhove
Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination...
April 9, 2024: Cell reports medicine
#38
JOURNAL ARTICLE
Zuping Wang, Heyrim Cho, Peter Choyke, Doron Levy, Noriko Sato
Engineered T cell receptor (TCR)-expressing T (TCR-T) cells are intended to drive strong anti-tumor responses upon recognition of the specific cancer antigen, resulting in rapid expansion in the number of TCR-T cells and enhanced cytotoxic functions, causing cancer cell death. However, although TCR-T cell therapy against cancers has shown promising results, it remains difficult to predict which patients will benefit from such therapy. We develop a mathematical model to identify mechanisms associated with an insufficient response in a mouse cancer model...
April 16, 2024: Bulletin of Mathematical Biology
#39
JOURNAL ARTICLE
Shiliang Cheng, Meng Li, Chunguang Li, Yonggang Dai, Jinhua Zhuo, Jue Wang, Jingrong Qian, Zhihao Hao
It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers...
April 16, 2024: In Vitro Cellular & Developmental Biology. Animal
#40
JOURNAL ARTICLE
Hannah W Song, Michaela Prochazkova, Lipei Shao, Roshini Traynor, Sarah Underwood, Mary Black, Vicki Fellowes, Rongye Shi, Marie Pouzolles, Hsien-Chao Chou, Adam T Cheuk, Naomi Taylor, Ping Jin, Robert P Somerville, David F Stroncek, Javed Khan, Steven L Highfill
With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and function are key attributes that often correlate with therapeutic efficacy, how manufacturing platforms influence the final CAR-T cell product is currently unknown...
March 12, 2024: Cytotherapy
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