keyword
https://read.qxmd.com/read/38386917/altered-cd226-tigit-expressions-were-associated-with-activated-nk-phenotypes-in-primary-anti-phospholipid-syndrome-and-affected-by-il-4-jak-pathway
#21
JOURNAL ARTICLE
Yan Long, Ke-Jia Lu, Chang-Sheng Xia, Jing-Hong Feng, Wen-Yi Li, Yin-Ting Ma, Yuan-Yuan Sun, Chun-Hong Fan, Chun Li
Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor TIGIT and activating receptor CD226 are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS...
February 22, 2024: Clinical and Experimental Immunology
https://read.qxmd.com/read/38375475/immune-checkpoint-inhibitors-associated-cardiovascular-immune-related-adverse-events
#22
REVIEW
Wonyoung Jo, Taejoon Won, Abdel Daoud, Daniela Čiháková
Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38359047/characterization-of-covalent-inhibitors-that-disrupt-the-interaction-between-the-tandem-sh2-domains-of-syk-and-fcer1g-phospho-itam
#23
JOURNAL ARTICLE
Frances M Bashore, Vittorio L Katis, Yuhong Du, Arunima Sikdar, Dongxue Wang, William J Bradshaw, Karolina A Rygiel, Tina M Leisner, Rod Chalk, Swati Mishra, C Andrew Williams, Opher Gileadi, Paul E Brennan, Jesse C Wiley, Jake Gockley, Gregory A Cary, Gregory W Carter, Jessica E Young, Kenneth H Pearce, Haian Fu, Alison D Axtman
RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer's disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor tyrosine-based activation motif (ITAM). SYK interacts with the Fc receptor by binding to doubly phosphorylated ITAM (p-ITAM) via its two tandem SH2 domains (SYK-tSH2). Interaction of the FCER1G p-ITAM with SYK-tSH2 enables SYK activation via phosphorylation...
2024: PloS One
https://read.qxmd.com/read/38324591/adaptive-design-of-nanovesicles-overcoming-immunotherapeutic-limitations-of-chemotherapeutic-drugs-through-poliovirus-receptor-blockade
#24
JOURNAL ARTICLE
Yongkang Yu, Fan Zhang, Wenqing Xiao, Qinzhen Cheng, Tingxuan Li, Jing Tang, Wei Tao, Lin Mei
Chemotherapy is currently a widely used treatment for cancer in clinical settings. Some chemotherapeutic drugs such as oxaliplatin (OXA) can cause tumor immunogenic cell death (ICD), activate immunity, and realize chemoimmunotherapy for tumors. However, the low degree of accumulation and immunosuppressive microenvironment in tumors limit the immunotherapeutic efficacy of these drugs. T cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor (PVR) is an inhibitory immune checkpoint pathway involved in mediating natural killer (NK) cell and T cell exhaustion in tumors...
February 7, 2024: ACS Nano
https://read.qxmd.com/read/38323498/differential-immunoexpression-of-inhibitory-immune-checkpoint-molecules-and-clinicopathological-correlates-in-keratoacanthoma-primary-cutaneous-squamous-cell-carcinoma-and-metastases
#25
JOURNAL ARTICLE
Anke S Lonsdorf, Dominic Edelmann, Thomas Albrecht, Alexander Brobeil, Jannik Labrenz, Moritz Johanning, Richard F Schlenk, Benjamin Goeppert, Alexander H Enk, Ferdinand Toberer
Beyond established anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) and its ligand CD155 are promising novel inhibitory immune checkpoint targets in human malignancies. Yet, in cutaneous squamous cell carcinoma, evidence on the collective expression patterns of these inhibitory immune checkpoints is scarce. Complete tumour sections of 36 cutaneous squamous cell carcinoma, 5 cutaneous metastases and 9 keratoacanthomas, a highly-differentiated, squamoproliferative tumour, with disparately benign biologic behaviour, were evaluated by immunohistochemistry for expression of programmed cell death ligand 1 (Tumor Proportion Score, Immune Cell Score), TIGIT, CD155 and CD8+ immune infiltrates...
February 7, 2024: Acta Dermato-venereologica
https://read.qxmd.com/read/38310035/star-121-a-phase-iii-randomized-study-of-domvanalimab-and-zimberelimab-in-combination-with-chemotherapy-versus-pembrolizumab-with-chemotherapy-in-untreated-metastatic-non-small-cell-lung-cancer-with-no-actionable-gene-alterations
#26
JOURNAL ARTICLE
Delvys Rodriguez-Abreu, Joaquim Bosch-Barrera, Jhanelle E Gray, Myung-Ju Ahn, Melissa Johnson, Xinwei Yu, Saad Mohammad, Xueying Chen, Trever Todd, Jongseok Kim, Martin Reck
INTRODUCTION: Dual inhibition with a T-cell immunoreceptor with immunoglobulin and ITIM domains plus programmed death (ligand)-1 (PD[L]-1) inhibitors, with or without chemotherapy, is an emerging therapeutic strategy in metastatic non-small cell lung cancer (mNSCLC). The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti-PD-1) plus chemotherapy versus pembrolizumab plus chemotherapy in mNSCLC with no actionable gene alterations...
January 6, 2024: Clinical Lung Cancer
https://read.qxmd.com/read/38305286/ectopic-expression-of-tigit-in-lung-adenocarcinoma-and-its-clinical-significance
#27
JOURNAL ARTICLE
Shuyan He, Ning Qian, Shujuan Ren, Chenglong Ma, Dong Shen, Ye Tian
This study aimed to investigate the T cell immunoreceptor with ITIM and Ig domains (TIGIT) expression in lung adenocarcinoma (LUAD). TIGIT expression was measured by western blot, reverse transcription quantitative polymerase chain reaction. Seventy-two paired surgical specimens were collected from patients with stage I-IV LUAD. The expression of TIGIT in surgical specimens was determined using immunohistochemistry. TIGIT was overexpressed in LUAD tissues. Moreover, overexpressed TIGIT was significantly associated with advanced clinical staging, lymph node metastasis, distant metastasis, and TP53 mutations in LUAD...
2024: Critical Reviews in Eukaryotic Gene Expression
https://read.qxmd.com/read/38301504/il-23-induces-clec5a-il-17a-neutrophils-and-elicit-skin-inflammation-associated-with-psoriatic-arthritis
#28
JOURNAL ARTICLE
Hiroki Furuya, Cuong Thach Nguyen, Trevor Chan, Alina I Marusina, Alexander A Merleev, Maria de la Luz Garcia-Hernandez, Shie-Liang Hsieh, George C Tsokos, Christopher T Ritchlin, Ilias Tagkopoulos, Emanual Maverakis, Iannis E Adamopoulos
IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23RGFP reporter mice and subsequent analysis with spectral cytometry show that IL-23 regulates early innate immune events by inducing the expansion of a myeloid MDL1+ CD11b+ Ly6G+ population that dictates epidermal hyperplasia, acanthosis, and parakeratosis; hallmark pathologic features of psoriasis...
January 31, 2024: Journal of Autoimmunity
https://read.qxmd.com/read/38291414/t-cell-immunoglobulin-and-immunoreceptor-tyrosine-based-inhibitory-motif-domain-as-a-promising-immune-checkpoint-target-for-the-treatment-of-sle
#29
REVIEW
Junpeng Zhao, Liming Li, Xiwei Feng, Xinyu Fan, Huiqi Yin, Qianjin Lu
Immune checkpoints (ICs) play a pivotal role in orchestrating immune regulation, crucial for the maintenance of immune tolerance and prevention of autoimmune diseases. One noteworthy example among these immune regulators is T cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT). The TIGIT pathway's inhibition or the absence of TIGIT has been linked to the hyperactivation and excessive proliferation of T cells, rendering individuals more susceptible to autoimmune diseases and exacerbating inflammatory responses...
March 2024: Lupus
https://read.qxmd.com/read/38290769/combination-of-oligo-fractionated-irradiation-with-nivolumab-can-induce-immune-modulation-in-gastric-cancer
#30
JOURNAL ARTICLE
Kosaku Mimura, Takashi Ogata, Phuong H D Nguyen, Souvick Roy, Hassen Kared, Yate-Ching Yuan, Michael Fehlings, Yuya Yoshimoto, Daisaku Yoshida, Shotaro Nakajima, Hisashi Sato, Nozomu Machida, Takanobu Yamada, Yohei Watanabe, Tomoaki Tamaki, Hirohito Fujikawa, Yasuhiro Inokuchi, Suguru Hayase, Hiroyuki Hanayama, Zenichiro Saze, Hiroyuki Katoh, Fumiaki Takahashi, Takashi Oshima, Ajay Goel, Alessandra Nardin, Yoshiyuki Suzuki, Koji Kono
BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164)...
January 30, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38289706/essential-role-of-cd155-glycosylation-in-functional-binding-to-dnam-1-on-natural-killer-cells
#31
JOURNAL ARTICLE
Saeko Tahara, Genki Okumura, Tomohei Matsuo, Akira Shibuya, Kazuko Shibuya
CD155 is highly expressed on tumor cells and augments or inhibits the cytotoxic activities of natural killer (NK) cells and T cells through its receptor ligands DNAM-1 and T cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), respectively. Although CD155 is heavily glycosylated, the role of glycosylation of CD155 in the cytotoxic activity of effector lymphocytes remains unknown. Here, we show that the N-linked glycosylation at residue 105 (N105 glycosylation) in the first immunoglobulin-like domain of CD155 is involved in the binding of CD155 to both DNAM-1 and TIGIT...
January 30, 2024: International Immunology
https://read.qxmd.com/read/38279870/combining-tigit-blockade-with-il-15-stimulation-is-a-promising-immunotherapy-strategy-for-lung-adenocarcinoma
#32
JOURNAL ARTICLE
Baohong Luo, Yu Sun, Qinru Zhan, Yuting Luo, Yu Chen, Tongze Fu, Tiantian Yang, Lijuan Ren, Zhongpeng Xie, Xiaohua Situ, Bixia Liu, Kejing Tang, Zunfu Ke
BACKGROUND: T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune checkpoint molecule that suppresses CD8+ T-cell function in cancer. However, the expression profile and functional significance of TIGIT in the immune microenvironment of lung adenocarcinoma (LUAD) remain elusive. Interleukin (IL)-15 has emerged as a promising candidate for enhancing CD8+ T-cell mediated tumour eradication. Exploring therapeutic strategies that combine IL-15 with TIGIT blockade in LUAD is warranted...
January 2024: Clinical and Translational Medicine
https://read.qxmd.com/read/38236412/restraining-of-glycoprotein-vi-and-integrin-%C3%AE-2%C3%AE-1-dependent-thrombus-formation-by-platelet-pecam1
#33
JOURNAL ARTICLE
Natalie J Jooss, Marije G Diender, Delia I Fernández, Jingnan Huang, Floor C J Heubel-Moenen, Arian van der Veer, Marijke J E Kuijpers, Natalie S Poulter, Yvonne M C Henskens, Maroeska Te Loo, Johan W M Heemskerk
The platelet receptors, glycoprotein VI (GPVI) and integrin α2β1 jointly control collagen-dependent thrombus formation via protein tyrosine kinases. It is unresolved to which extent the ITIM (immunoreceptor tyrosine-based inhibitory motif) receptor PECAM1 and its downstream acting protein tyrosine phosphatase PTPN11 interfere in this process. Here, we hypothesized that integrin α2β1 has a co-regulatory role in the PECAM1- and PTPN11-dependent restraint of thrombus formation. We investigated platelet activation under flow on collagens with a different GPVI dependency and using integrin α2β1 blockage...
January 18, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38235377/fc-gamma-receptors-promote-antibody-induced-lilrb4-internalization-and-immune-regulation-of-monocytic-aml
#34
JOURNAL ARTICLE
Joshua W Morse, Xun Gui, Mi Deng, Ryan Huang, Xiaohua Ye, Peng Zhao, Xuejun Fan, Wei Xiong, Chengcheng Zhang, Ningyan Zhang, Zhiqiang An
The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40-60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs)...
January 2024: Antibody Therapeutics
https://read.qxmd.com/read/38233101/lower-frequencies-of-circulating-suppressive-regulatory-t-cells-and-higher-frequencies-of-cd4-na%C3%A3-ve-t-cells-at-baseline-are-associated-with-severe-immune-related-adverse-events-in-immune-checkpoint-inhibitor-treated-melanoma
#35
JOURNAL ARTICLE
Magdalena Kovacsovics-Bankowski, Johanna M Sweere, Connor P Healy, Natalia Sigal, Li-Chun Cheng, William D Chronister, Shane A Evans, John Marsiglio, Berit Gibson, Umang Swami, Alyssa Erickson-Wayman, Jordan P McPherson, Yoko S Derose, Annaleah Larson Eliason, Carlos O Medina, Ramji Srinivasan, Matthew H Spitzer, Ngan Nguyen, John Hyngstrom, Siwen Hu-Lieskovan
BACKGROUND: Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention. METHODS: We used a 43-marker mass cytometry panel to characterize peripheral blood mononuclear cells from 28 unique patients with melanoma across 29 lines of ICI therapy before treatment (baseline), before the onset of irAEs (pre-irAE) and at the peak of irAEs (irAE-max)...
January 17, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38229100/targeting-tigit-for-cancer-immunotherapy-recent-advances-and-future-directions
#36
REVIEW
Peng Zhang, Xinyuan Liu, Zhuoyu Gu, Zhongxing Jiang, Song Zhao, Yongping Song, Jifeng Yu
As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT...
January 16, 2024: Biomarker Research
https://read.qxmd.com/read/38226018/immune-checkpoint-expression-patterns-on-t-cell-subsets-in-light-chain-amyloidosis-vista-pd-1-and-tigit-as-potential-therapeutic-targets
#37
JOURNAL ARTICLE
Jinghua Wang, Yujie Zhao, Pengjun Liao, Shuxin Huang, Youxue Huang, Shaohua Chen, Yangqiu Li, Liye Zhong
Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+ ), programmed cell death 1+ (PD-1+ ), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+ ), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+ ) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis...
January 2024: Blood Sci
https://read.qxmd.com/read/38219557/synthetic-studies-on-the-extracellular-domain-of-the-t-cell-immunoreceptor-with-immunoglobulin-and-immunoreceptor-tyrosine-based-inhibitory-motif-domain-tigit-using-trt-k-10-solubilizing-tags
#38
JOURNAL ARTICLE
Naoya Iwamoto, Jumpei Sasaki, Saya Ohno, Keisuke Aoki, Yusuke Usui, Shinsuke Inuki, Hiroaki Ohno, Shinya Oishi
The T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immunoreceptor expressed on lymphocytes that serves as a promising target for cancer immunotherapy. In this study, facile synthetic protocols to produce the extracellular domain of TIGIT were investigated for applications of TIGIT in mirror-image screening. During the synthesis via sequential native chemical ligations, we encountered problems with significantly poor solubility of the ligated products...
December 30, 2023: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/38215579/controling-the-cytoskeleton-during-ceacam3-mediated-phagocytosis
#39
JOURNAL ARTICLE
Johannes W P Kuiper, Helena L Gregg, Meike Schüber, Jule Klein, Christof R Hauck
Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the fastest evolving human proteins implying a special role in human biology. This receptor, CEACAM3, is a member of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule (CEACAM) family and dedicated to the immediate recognition and rapid internalization of human-restricted pathogens...
January 5, 2024: European Journal of Cell Biology
https://read.qxmd.com/read/38206370/phase-i-study-of-the-anti-tigit-antibody-tiragolumab-in-combination-with-atezolizumab-in-japanese-patients-with-advanced-or-metastatic-solid-tumors
#40
JOURNAL ARTICLE
Noboru Yamamoto, Takafumi Koyama, Jun Sato, Tatsuya Yoshida, Kazuki Sudo, Satoru Iwasa, Shunsuke Kondo, Kan Yonemori, Atsuko Kawasaki, Kyoko Satake, Shoyo Shibata, Toshio Shimizu
PURPOSE: Tiragolumab is a monoclonal antibody that binds to the inhibitory immune checkpoint TIGIT (T-cell immunoreceptor with Ig and ITIM domains). In early phase clinical trials, tiragolumab in combination with the programmed death-ligand 1-inhibitor atezolizumab was well tolerated and has demonstrated preliminary anti-tumor activity in patients with advanced/metastatic solid tumors. We report the results of a phase I study of tiragolumab plus atezolizumab in Japanese patients (jRCT2080224926)...
January 11, 2024: Cancer Chemotherapy and Pharmacology
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