Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics f... by Aliosha I. Figueroa-Valdés, Patricia Luz-Crawford, Yeimi Herrera-Luna, Nicolás Georges-Calderón, Cynthia García, Hugo E. Tobar, María Jesús Araya, José Matas, Darío Donoso-Meneses, Catalina de la Fuente, Jimena Cuenca, Eliseo Parra, Fernando Lillo, Cristóbal Varela, María Ignacia Cádiz, Rolando Vernal, Alexander Ortloff, Gino Nardocci, Verónica Castañeda, Catalina Adasme-Vidal, Maximiliano Kunze-Küllmer, Yessia Hidalgo, Francisco Espinoza, Maroun Khoury, Francisca Alcayaga-Miranda

“…In silico studies confirmed sEV's immunosuppressive signature through miRNA and proteome analysis. …”
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Differentiation status determines the effects of IFNγ on the expression of PD-L1 and immunomodulatory genes in melanoma by Teitur Sævarsson, Adrián López García de Lomana, Ólafur Sánchez, Veerle van Esch, Gunnar Bjarni Ragnarsson, Siggeir Fannar Brynjólfsson, Eiríkur Steingrímsson, Berglind Ósk Einarsdóttir

“…Interferon-γ (IFNγ) is an integral part of the anti-tumor immune response and can directly induce both differentiational changes and expression of immunosuppressive proteins in melanoma cells. How the differentiation status of melanoma cells affects IFNγ responses remains unclear. …”
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TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial by Wei Gao, Ping Hu, Aung Naing, Meredith McKean, Anthony Tolcher, Lillian L Siu, Keyvan Tadjalli-Mehr, Anja Victor, Emilia Richter, Marco A F Nogueira Filho, Thomas Kitzing, Stephan Gleicher, Daniel Holland

“…Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.Methods This first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10–2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300–1600 mg with BA 1200 mg; both every 2 weeks, intravenous). …”
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Clinical experience with cyclosporine eye drops for severe dry eye by O.I. Lebedev, A.V. Surov, E.V. Akentieva

“…Vykhodtsev, Omsk, Russian Federation<br> <br> Dry eye disease provokes inflammation of autoimmune origin. Therefore, immunosuppressants are pathogenetically reasonable for this disorder. …”
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Integrating single-cell RNA-Seq and bulk RNA-Seq data to explore the key role of fatty acid metabolism in hepatocellular carcinoma by Hua Dai, Xin Tao, Yuansen Shu, Fanrong Liu, Xiaoping Cheng, Xiushen Li, Bairui Shu, Hongcheng Luo, XuXiang Chen, Zhaorui Cheng

“…Elevated expression of PTGES3 was linked to immunosuppressive cascades, diminished responsiveness to immunotherapy, and inferior overall survival outcomes. …”
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Clinical Features, Endoscopic Findings, and Predictive Factors for Mortality in Tissue-Invasive Gastrointestinal Cytomegalovirus Disease between Immunocompetent and Immunocompromis... by Panu Wetwittayakhlang, Natthapat Rujeerapaiboon, Poowadon Wetwittayakhlung, Pimsiri Sripongpun, Nannapat Pruphetkaew, Sawangpong Jandee, Naichaya Chamroonkul, Teerha Piratvisuth

“…Patients with HIV infection, malignancy, or receiving immunosuppressive agents (chemotherapy, high dose, or long-term corticosteroids) were defined as the immunocompromised group. …”
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COVID-19 pandemic and vaccination rate in patients with psoriasis treated with biologics: A single center experience by Milčić Danijela, Malinić Marija, Ćirković Anđa, Krupniković Doroteja, Milinković-Srećković Mirjana

“…The coronavirus disease 2019 (COVID-19) raised widespread concern for patients with psoriasis treated with immunosuppressive drugs, especially biologics. Even though there was no data at the beginning of the pandemic on the efficacy and safety of vaccines against COVID-19 in patients with psoriasis treated with biologics, the National Psoriasis Foundation (United States of America) recommended vaccination in these patients. …”
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Differential impact of TIM-3 ligands on NK cell function by Xin Zhang, Lazar Vujanovic, Riyue Bao, Robert L Ferris, Tullia C Bruno, Aditi Kulkarni, Hridesh Banerjee, Housaiyin Li, Juncheng Wang, Lawrence P Kane, Pragati Upadhyay, Jennifer L Anderson, Onyedikachi Victor Onyekachi, Lidia M R B Arantes

“…The primary objectives of this study were to assess the prevalence and function of TIM-3+ natural killer (NK) cells in patients with head and neck squamous cell carcinoma (HNSCC), determine whether the four TIM-3 ligands differentially affect TIM-3+ NK cell functions, identify the most immunosuppressive ligand, and evaluate whether targeting ligand-mediated TIM-3 signaling enhances NK cell effector functions.Methods Single-cell RNA sequencing and flow cytometry were used to study the prevalence, phenotypes and function of TIM-3+ NK cells in HNSCC patient tumors and blood. …”
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Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open‐Label Trial by Orrin M. Troum, John K. Botson, Katie Obermeyer, Bo Chao, Yang Song, Jennifer Zarzoso, Kjerstina Gutierrez, Supra Verma, Lissa Padnick‐Silver, Brian LaMoreaux

“…Key exclusion criteria were moderate‐to‐severe IR or anaphylaxis to pegloticase, MTX contraindication, immunosuppressant administration, glucose‐6‐phosphate dehydrogenase deficiency, and estimated glomerular filtration rate <30 mL/min/1.73m2. …”
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Clinical and analytical monitoring of patients with multiple sclerosis on anti-CD20 therapeutics: a real-world safety profile study by André Aires Fernandes, André Aires Fernandes, Ana Lídia Neves, Ana Lídia Neves, Daniela Ferro, Daniela Ferro, Mafalda Seabra, Mafalda Seabra, Teresa Mendonça, Ricardo Soares dos Reis, Ricardo Soares dos Reis, Maria José Sá, Joana Guimarães, Joana Guimarães, Pedro Abreu, Pedro Abreu

“…BackgroundAnti-CD20 monoclonal antibodies are a class of immunosuppressive drugs widely used in the treatment of central nervous system (CNS) inflammatory diseases, with well-established efficacy and safety. …”
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Diagnostic Effectiveness of Transforming Growth Factor Beta 1 in Assessing the Risk of Developing Graft Dysfunction in Liver Recipient Children by R. M. Kurabekova, O. M. Tsiroulnikova, I. E. Pashkova, A. G. Olefirenko, O. E. Gichkun, L. V. Makarova, R. A. Monakhov, P. O. Shevchenko

“…Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with a profibrogenic and immunosuppressive effect that can have a definite effect on the liver transplant functioning.Aim. …”
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29 m6A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset... by Ming Liu, Keman Xu, Fatma Saaoud, Ying Shao, Ruijing Zhang, Yifan Lu, Yu Sun, Charles Drummer, Li Li, Sheng Wu, Satya P. Kunapuli, Gerard J. Criner, Jianxin Sun, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

“…We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. …”
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Krebs von den Lungen-6 surveillance in immune checkpoint inhibitor-induced pneumonitis by Isamu Okamoto, Kazuya Tsubouchi, Ryosuke Matsukane, Shoji Nakamura, Haruna Minami, Yasuto Yoneshima, Kojiro Hata, Sai Yasukochi, Kimitaka Suetsugu, Takeshi Hirota

“…Early detection through KL-6 monitoring facilitates timely intervention for ICI-induced pneumonitis, potentially preventing treatment interruptions and reducing the need for immunosuppressants.…”
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Drug-drug interaction between ensitrelvir and tacrolimus in a patient undergoing treatment for COVID-19: a case report by Yuki Miyata, Ryo Yamaguchi, Takehito Yamamoto, Toshiyuki Kishida, Kazuhiko Ikeuchi, Hiroaki Harada, Takeya Tsutsumi, Keishi Fujio, Tappei Takada

“…Tacrolimus (TAC) is a widely used immunosuppressive agent whose blood level can increase significantly due to the inhibition of cytochrome P450 3A (CYP3A) and P-glycoprotein by nirmatrelvir/ritonavir. …”
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SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report by Hongyan Liu, Colleen Callahan, Shannon L Maude, Kevin Owen McNerney, Rebecca M Richards, Paibel Aguayo-Hiraldo, Friso G Calkoen, Julie-An Talano, Amy Moskop, Adriana Balduzzi, Jennifer Krajewski, Hema Dave, Anant Vatsayan, Yimei Li, Kara Lynn Davis

“…Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). …”
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4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models by Ignacio Melero, Alvaro Teijeira, Christian Klein, Maria E Rodriguez-Ruiz, Christina Claus, Pablo Umana, Tamara Tanos, Carlos E De Andrea, Carlos Luri-Rey, Paloma Sanchez-Mateos, Leticia Fernández-Rubio, María Collantes, Irantzu Serrano-Mendioroz, Celia Barrio-Alonso, Antonio Rullan, Jon Ander Simon, Eneko Garate-Soraluze, Claudia del Pilar Herrero

“…Background Ionizing radiation (IR) is a double-edged sword for immunotherapy as it may have both immunosuppressive and immunostimulatory effects. The biological effects of IR on the tumor microenvironment (TME) are a key factor for this balance. …”
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Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway by Yan Li, Hong Wang, Xiaoyang Li, Yuan He, Huiquan Liu, Dong Han, Ting Mei, Yixuan Li, Zilong Xu, Xiaoying Wei, Jianguo Wang, Peijie Zhou, Yuwen Wang, Ziye Li, Junhao Ning, Anlin Wang, Jingjing Cheng, Dong Qian

“…Background Immunosuppressive phenotype compromised immunotherapy efficacy of hepatocellular carcinoma. …”
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The Effects of Mesenchymal Stem Cells on Antimelanoma Immunity Depend on the Timing of Their Administration by Dragana Miloradovic, Dragica Miloradovic, Bojana Simovic Markovic, Aleksandar Acovic, Carl Randall Harrell, Valentin Djonov, Nebojsa Arsenijevic, Vladislav Volarevic

“…Significantly higher plasma levels of antitumorigenic cytokines (TNF-α and IFN-γ), remarkably lower plasma levels of immunosuppressive cytokines (TGF-β and IL-10), and a significantly higher number of tumor-infiltrating, IFN-γ-producing, FasL- and granzyme B-expressing NK cells, IL-17-producing CD4+Th17 cells, IFN-γ- and TNF-α-producing CD4+Th1 cells, and CD8+cytotoxic T lymphocytes (CTLs) were observed in B16F10+MSC1d-treated mice. …”
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Arginase-1-specific T cells target and modulate tumor-associated macrophages by Mads Hald Andersen, Inés Lecoq, Ayako Wakatsuki Pedersen, Evelina Martinenaite, Shamaila Munir Ahmad, Maria Perez-Penco, Lucia Lara de la Torre, Marion Chapellier, Lars Rønn Olsen, Mia Aaboe-Jørgensen, Hannah Jorinde Glöckner, Anne Mette Askehøj Rømer

“…The effect of Arg1-derived peptide IMV on TAMs in vivo was assessed by multiplex gene analysis of F4/80+cells.Results We show that Arg1-based IMV-mediated tumor control was linked to a decrease in multiple immunosuppressive pathways in the TAM population of the treated animals. …”
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Distribution of Airway Findings in ANCA-Associated Vasculitis: A 20-Year Observational Analysis by Megan M. Sullivan, Maximiliano Diaz Menindez, Hassan Baig, Anushka Irani, Ronald Butendieck, Benjamin Wang, Florentina Berianu, Carolyn Mead-Harvey, Andy Abril, Vikas Majithia

“…The primary outcome was time to relapse of the tracheobronchial inflammation after starting immunosuppressive medication, analyzed using the Kaplan–Meier method and log-rank tests. …”
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