keyword
https://read.qxmd.com/read/38336861/immunological-characterization-of-a-long-lasting-response-in-a-patient-with-metastatic-triple-negative-breast-cancer-treated-with-pd-1-and-lag-3-blockade
#21
JOURNAL ARTICLE
Licia Rivoltini, Chiara Camisaschi, Giovanni Fucà, Biagio Paolini, Barbara Vergani, Valeria Beretta, Silvia Damian, Matteo Duca, Sara Cresta, Michele Magni, Biagio Eugenio Leone, Chiara Castelli, Filippo de Braud, Francesca De Santis, Massimo Di Nicola
In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression...
February 9, 2024: Scientific Reports
https://read.qxmd.com/read/38336764/tfrc-associated-with-hypoxia-and-immune-is-a-prognostic-factor-and-potential-therapeutic-target-for-bladder-cancer
#22
JOURNAL ARTICLE
Runhua Tang, Haoran Wang, Jianyong Liu, Liuqi Song, Huimin Hou, Ming Liu, Jianye Wang, Jianlong Wang
BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA...
February 9, 2024: European Journal of Medical Research
https://read.qxmd.com/read/38327094/lymphocyte-activation-gene-3-facilitates-pathological-tau-neuron-to-neuron-transmission
#23
JOURNAL ARTICLE
Chan Chen, Ramhari Kumbhar, Hu Wang, Xiuli Yang, Kundlik Gadhave, Cyrus Rastegar, Yasuyoshi Kimura, Adam Behensky, Sumasri Kotha, Grace Kuo, Sruthi Katakam, Deok Jeong, Liang Wang, Anthony Wang, Rong Chen, Shu Zhang, Lingtao Jin, Creg J Workman, Dario A A Vignali, Olga Pletinkova, Hongpeng Jia, Weiyi Peng, David W Nauen, Philip C Wong, Javier Redding-Ochoa, Juan C Troncoso, Mingyao Ying, Valina L Dawson, Ted M Dawson, Xiaobo Mao
The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau...
February 7, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38324004/tumor-infiltrating-%C3%AE-%C3%AE-t-cells-as-targets-of-immune-checkpoint-blockade-in-melanoma
#24
JOURNAL ARTICLE
Marta Di Simone, Anna Maria Corsale, Francesca Toia, Mojtaba Shekarkar Azgomi, Anna Barbara Di Stefano, Elena Lo Presti, Adriana Cordova, Luigi Montesano, Francesco Dieli, Serena Meraviglia
Melanoma is one of the most sensitive tumors to immune modulation and the major challenge for melanoma patients' survival is immune checkpoint inhibitors therapy. γδ T lymphocytes play an antitumoral role in a broad variety of tumors including melanoma and they are optimal candidates for cellular immunotherapy. Thus, a comprehensive analysis of the correlation between γδ T cells and immune checkpoint receptors in the context of melanoma was conducted, with the aim of devising an innovative combined immunotherapeutic strategy...
February 7, 2024: Journal of Leukocyte Biology
https://read.qxmd.com/read/38322766/combinatorial-immune-checkpoint-blockade-increases-myocardial-expression-of-nlrp-3-and-secretion-of-h-fabp-nt-pro-bnp-interleukin-1%C3%AE-and-interleukin-6-biochemical-implications-in-cardio-immuno-oncology
#25
JOURNAL ARTICLE
V Quagliariello, M Passariello, I Bisceglia, A Paccone, A Inno, C Maurea, R Rapuano Lembo, L Manna, M Iovine, M L Canale, M Scherillo, P A Ascierto, D Gabrielli, C De Lorenzo, N Maurea
BACKGROUND: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer...
2024: Frontiers in Cardiovascular Medicine
https://read.qxmd.com/read/38299081/bilateral-paracentral-corneal-melting-and-left-eye-perforation-under-tobemstomig-novel-treatment
#26
Pablo González de Los Mártires, Gonzalo Guerrero Pérez, Nerea Gangoitia Gorrotxategi, Iñigo Salmerón Garmendia, Leire Olazaran Gamboa, Ana Jiménez Alonso, Lara Berástegui Arbeloa
INTRODUCTION: We present a rare occurrence of bilateral corneal melting and a left-eye corneal perforation in an oncologic patient undergoing a new biological therapy. CASE PRESENTATION: A 63-year-old male with a two-day history of a painful left red eye and bilateral visual impairment was enrolled in a multicenter phase-II study comparing tobemstomig/RO7247669, a PD1-LAG3 bispecific antibody, with nivolumab. Clinical examination revealed a bilateral central corneal thinning, and corneal OCT imaging indicated a significant stromal thinning of 124 μm in the right eye and a central corneal perforation of 286 μm in the left eye...
2024: Case Reports in Ophthalmology
https://read.qxmd.com/read/38295929/association-of-short-term-pm-2-5-exposure-with-airway-innate-immune-response-microbiota-and-metabolism-alterations-in-human-airways
#27
JOURNAL ARTICLE
Shuaiqi Zhao, Huijun Li, Fuyun Yang, Yishu Yang, Yuling Zeng, Zhen An, Juan Li, Hui Wu, Jie Song, Weidong Wu
Exposure to fine particulate matter (PM2.5 ) has been associated with impaired airway innate immunity, leading to diverse lung disorders. However, the mechanisms of the adverse effects of PM2.5 on the airway innate immune system has not been adequately elucidated. This study aimed to investigate the association between short-term exposure to ambient PM2.5 and airway innate immune responses. A panel study of 53 undergraduate students was conducted in November 2020 and April 2021. Levels of airway innate immune biomarkers including interleukin-1β (IL-1β), IL-4, IL-6, IL-8, IL-17, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) in induced sputum were measured, and airway microbiota and metabolites examined...
January 29, 2024: Environmental Pollution
https://read.qxmd.com/read/38294292/first-line-immunotherapy-in-non-small-cell-lung-cancer-how-to-select-and-where-to-go
#28
REVIEW
Andrea Mogavero, Ornella Cantale, Veronica Mollica, Shobana Anpalakhan, Alfredo Addeo, Giannis Mountzios, Alex Friedlaender, Ravindran Kanesvaran, Silvia Novello, Giuseppe Luigi Banna
INTRODUCTION: Immunotherapy (IO) has established a new milestone in lung cancer treatment. Several registrational studies have approved immune checkpoint inhibitors (ICIs) in different settings, including the metastatic nonsmall cell lung cancer (NSCLC). As wellknown, responders are just a certain proportion of patients, therefore their selection by using predictive factors has stood out as a crucial issue to address in tailoring a patientcentered care. AREAS COVERED: In our review we propose a detailed yet handy cross section on ICIs as firstline treatment in metastatic NSCLC, regarding indications, histological, clinical and bloodbased biomarkers, other than their mechanisms of resistance and new immunological actionable targets...
January 31, 2024: Expert Review of Respiratory Medicine
https://read.qxmd.com/read/38293085/integrated-germline-and-somatic-features-reveal-divergent-immune-pathways-driving-icb-response
#29
Timothy Sears, Meghana Pagadala, Andrea Castro, Ko-Han Lee, JungHo Kong, Kairi Tanaka, Scott Lippman, Maurizio Zanetti, Hannah Carter
UNLABELLED: Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. Here we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I). Further investigation uncovered different ICB responses in MHC-I versus MHC-II neoantigen reliant tumors across patients...
January 15, 2024: bioRxiv
https://read.qxmd.com/read/38291496/single-cell-combined-bioinformatics-analysis-construction-of-immune-cluster-and-risk-prognostic-model-in-kidney-renal-clear-cells-based-on-cd8-t-cell-associated-genes
#30
JOURNAL ARTICLE
Haifeng Gao, Hang Sun, Aifeng He, Hui Liu, Zihang Zhang, Dongling Li, Weipu Mao, Jinke Qian
BACKGROUND: Kidney cancer is an immunogenic solid tumor, characterized by high tumor burden and infiltration of CD8+ T cells. Although immunotherapy targeting the PD1/CTLA-4 axis has demonstrated excellent clinical efficacy, clinical outcomes in most patients are poor. METHODS: We used the RNA sequencing data from the GEO database for KIRC GSE121636 and normal kidney tissue GSE131685, and performed single-cell analysis for cluster identification, pathway enrichment, and CD8+ T cell-associated gene identification...
January 30, 2024: European Journal of Medical Research
https://read.qxmd.com/read/38280007/presence-of-epstein-barr-virus-ebv-antigens-detected-by-sensitive-methods-has-no-influence-on-local-immune-environment-in-diffuse-large-b-cell-lymphoma
#31
JOURNAL ARTICLE
T Mangiaterra, R Alonso-Alonso, A Rabinovich, M De Dios Soler, L Galluzzo, M Soria, S Colli, E De Matteo, S M Rodriguez Pinilla, P Chabay
EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL...
January 27, 2024: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/38280005/unraveling-t-cell-exhaustion-in-the-immune-microenvironment-of-osteosarcoma-via-single-cell-rna-transcriptome
#32
JOURNAL ARTICLE
Debin Cheng, Zhao Zhang, Dong Liu, Zhenzhou Mi, Weidong Tao, Jun Fu, Hongbin Fan
Osteosarcoma (OS) represents a profoundly invasive malignancy of the skeletal system. T cell exhaustion (Tex) is known to facilitate immunosuppression and tumor progression, but its role in OS remains unclear. In this study, single-cell RNA sequencing data was employed to identify exhausted T cells within the tumor immune microenvironment (TIME) of OS. We found that exhausted T cells exhibited substantial infiltration in OS samples. Pseudotime trajectory analysis revealed a progressive increase in the expression of various Tex marker genes, including PDCD1, CTLA4, LAG3, ENTPD1, and HAVCR2 in OS...
January 27, 2024: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/38278025/astragalus-polysaccharide-ameliorates-cd8-t-cell-dysfunction-through-stat3-gal-3-lag3-pathway-in-inflammation-induced-colorectal-cancer
#33
JOURNAL ARTICLE
Qiuyi Li, Chonghao Zhang, Guichuan Xu, Xuekai Shang, Xinmei Nan, Yalan Li, Jiajing Liu, Yanfei Hong, Qing Wang, Guiying Peng
Chronic inflammation can promote cancer development as observed in inflammation-induced colorectal cancer (CRC). However, the poor treatment outcomes emphasize the need for effective treatment. Astragalus polysaccharide (APS), a vital component of the natural drug Astragalus, has anti-tumor effects by inhibiting cancer cell proliferation and enhancing immune function. In this study, we found that APS effectively suppressed CRC development through activating CD8+ T cells and reversing its inhibitory state in the tumor microenvironment (TME) of AOM/DSS inflammation-induced CRC mice...
January 24, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38277212/integrative-analysis-of-lag3-immune-signature-and-identification-of-a-lag3-related-genes-prognostic-signature-in-kidney-renal-clear-cell-carcinoma
#34
JOURNAL ARTICLE
Jie Li, Chungan Liu, Hui Su, Hao Dong, Zhiqian Wang, Yuqi Wang, Peng Zhao, Chaowei Zhang, Yi Zhao, Xuezhen Ma
Immune checkpoint blockade (ICB) therapy has resulted in improved overall survival in kidney renal clear cell carcinoma (KIRC), but most treated patients fail to show durable clinical responses. Lymphocyte activation gene-3 (LAG3) is a novel inhibitory immune checkpoint, but its expression pattern, prognostic value, and immunological role in KIRC remain unknown. In this study, we utilized TCGA_KIRC RNA-sequencing data to analyze the relationship between LAG3 expression and clinical features. The single-cell sequencing data and tissue immunofluorescence are employed to investigate the subcellular localization of LAG3 in KIRC...
January 25, 2024: Aging
https://read.qxmd.com/read/38266804/neoadjuvant-chemotherapy-induced-remodeling-of-human-hormonal-receptor-positive-breast-cancer-revealed-by-single-cell-rna-sequencing
#35
JOURNAL ARTICLE
Fang Jia, Shanshan Sun, Jiaxin Li, Wenwen Wang, Huanhuan Huang, Xiaoxiao Hu, Sheng Pan, Wuzhen Chen, Lesang Shen, Yao Yao, Siwei Zheng, Hailong Chen, Wenjie Xia, Hongjun Yuan, Jun Zhou, Xiuyan Yu, Ting Zhang, Bing Zhang, Jian Huang, Chao Ni
Hormone receptor-positive breast cancer (HR + BC) is known to be relatively insensitive to chemotherapy, and since chemotherapy has remained the major neoadjuvant therapy for HR + BC, the undetermined mechanism of chemoresistance and how chemotherapy reshapes the immune microenvironment need to be explored by high-throughput technology. By using single-cell RNA sequencing and multiplexed immunofluorescence staining analysis of HR + BC samples (paired pre- and post-neoadjuvant chemotherapy (NAC)), the levels of previously unrecognized immune cell subsets, including CD8+ T cells with pronounced expression of T-cell development (LMNA) and cytotoxicity (FGFBP2) markers, CD4+ T cells characterized by proliferation marker (ATP1B3) expression and macrophages characterized by CD52 expression, were found to be increased post-NAC, which were predictive of chemosensitivity and their antitumor function was also validated with in vitro experiments...
January 22, 2024: Cancer Letters
https://read.qxmd.com/read/38255322/current-technologies-and-future-perspectives-in-immunotherapy-towards-a-clinical-oncology-approach
#36
REVIEW
Subhamay Adhikary, Surajit Pathak, Vignesh Palani, Ahmet Acar, Antara Banerjee, Nader I Al-Dewik, Musthafa Mohamed Essa, Sawsan G A A Mohammed, M Walid Qoronfleh
Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically...
January 18, 2024: Biomedicines
https://read.qxmd.com/read/38254772/beyond-pd-l-1-blockade-in-microsatellite-instable-cancers-current-landscape-of-immune-co-inhibitory-receptor-targeting
#37
REVIEW
Edoardo Crimini, Luca Boscolo Bielo, Pier Paolo Maria Berton Giachetti, Gloria Pellizzari, Gabriele Antonarelli, Beatrice Taurelli Salimbeni, Matteo Repetto, Carmen Belli, Giuseppe Curigliano
High microsatellite instability (MSI-H) derives from genomic hypermutability due to deficient mismatch repair function. Colorectal (CRC) and endometrial cancers (EC) are the tumor types that more often present MSI-H. Anti-PD(L)-1 antibodies have been demonstrated to be agnostically effective in patients with MSI-H cancer, but 50-60% of them do not respond to single-agent treatment, highlighting the necessity of expanding their treatment opportunities. Ipilimumab (anti-CTLA4) is the only immune checkpoint inhibitor (ICI) non-targeting PD(L)-1 that has been approved so far by the FDA for MSI-H cancer, namely, CRC in combination with nivolumab...
January 9, 2024: Cancers
https://read.qxmd.com/read/38244710/identification-of-cers5-as-a-molecular-biomarker-in-pan-cancer-through-multiple-omics-integrative-analysis
#38
JOURNAL ARTICLE
Shengyu Wang, Jian Yang, Weijia Huang, Zhu Yu, Yuantian Mao, Yue Feng, Junqiang Chen
Cancer is a devastating disease that presents a major threat to human health. The protein CERS5 is responsible for synthesizing C16-ceramide, but its role in cancer is poorly understood. In this study, we examined the connection between CERS5 expression and pan-cancer prognosis, diagnosis, and the molecular mechanism involved. Kaplan-Meier survival analysis revealed variations among different cancer types. Functional enrichment analysis was conducted using gene set enrichment analysis (GSEA), and a network of protein-protein interaction (PPI) was constructed...
January 18, 2024: Cellular Signalling
https://read.qxmd.com/read/38234210/clinicopathological-comparison-between-ptcl-tbx21-and-ptcl-gata3-in-japanese-patients
#39
JOURNAL ARTICLE
Yasumasa Shimasaki, Hiroaki Miyoshi, Keisuke Kawamoto, Noriaki Yoshida, Tatsuzo Mishina, Kazutaka Nakashima, Teppei Imamoto, Takeshi Sugio, Eriko Yanagida, Takeharu Kato, Kyohei Yamada, Mai Takeuchi, Takaharu Suzuki, Mayuko Moritsubo, Takuya Furuta, Yoshitaka Imaizumi, Jun Takizawa, Koji Kato, Junji Suzumiya, Ritsuro Suzuki, Koichi Ohshima
AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21)...
January 17, 2024: Cancer Medicine
https://read.qxmd.com/read/38203757/comparative-evaluation-of-steap1-targeting-chimeric-antigen-receptors-with-different-costimulatory-domains-and-spacers
#40
JOURNAL ARTICLE
Yixin Jin, Claire Dunn, Irene Persiconi, Adam Sike, Gjertrud Skorstad, Carole Beck, Jon Amund Kyte
We have developed a chimeric antigen receptor (CAR) against the six-transmembrane epithelial antigen of prostate-1 (STEAP1), which is expressed in prostate cancer, Ewing sarcoma, and other malignancies. In the present study, we investigated the effect of substituting costimulatory domains and spacers in this STEAP1 CAR. We cloned four CAR constructs with either CD28 or 4-1BB costimulatory domains, combined with a CD8a-spacer (sp) or a mutated IgG-spacer. The CAR T-cells were evaluated in short- and long-term in vitro T-cell assays, measuring cytokine production, tumor cell killing, and CAR T-cell expansion and phenotype...
January 2, 2024: International Journal of Molecular Sciences
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