tbuckley/cabot-search huggingface dataset:
Clinician views of patient navigators for underserved adults with asthma: A qualitative analysis
Authors: Andrea J Apter, Tyra Bryant-Stephens, Hami Park, Lenisha Fergus, Kadel LaRose, Philycia Foote, Freya Nezir, Anna U Morgan, Xiaoyan Han, Knashawn H Morales, Heather Klusaritz
Journal: Journal of Allergy and Clinical Immunology (2024)
Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis
Authors: Seung Kwon Koh, Hyojin Kim, Bohwa Han, Hantae Jo, Junsang Doh, Jeehun Park, Minh Ha Nguyen, Hyun-Young Kim, Haneul Kim, Seung-Hwan Lee, Chan Hyuk Kim, Duck Cho
Journal: Blood (2024)

Anti-CD19 chimeric antigen receptor (CAR)-engineered T and NK cell therapies have revolutionized the treatment of B cell malignancies, but challenges including CD19 antigen loss greatly hinder their full therapeutic potential. Here we demonstrated that co-treatment with anti-CD19 monoclonal antibody enhances antitumor activity of anti-CD19 CAR-T and -NK cells. Even though the treated antibody interferes with CD19 antigen binding of CAR, it significantly induces rapid detachment of anti-CD19 CAR effector cells from target cells, facilitating improved serial killing. This reduced interaction between CAR effector cells and target cells also leads to the alleviation of CAR-mediated trogocytosis. Interestingly, co-treatment with anti-CD19 antibody reveals time-dependent effects on the antitumor activity of anti-CD19 CAR-T cells, characterized by a reduction in early T cell activation followed by sustained high activity during prolonged exposure to target cells. This temporal modulation ultimately results in enhanced antitumor potency in vivo. These findings underscore the improved therapeutic efficacy achieved by combining anti-CD19 antibody with anti-CD19 CAR-T or -NK cells against B cell malignancies.
Corrigendum to “Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis and Re-polarization” [Biomaterials 264 (2021) 120390]
Authors: Yihua Yang, Lina Guo, Zhe Wang, Peng Liu, Xuanjun Liu, Jinsong Ding, Wenhu Zhou
Journal: Biomaterials (2024)
Efficacy and Safety of Venetoclax Plus Azacitidine for Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes
Authors: Jacqueline S. Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun A Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero
Journal: Blood (2024)
ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma
Authors: Mun Yee Koh, Tae-Hoon Chung, Nicole Xin Ning Tang, Sabrina Hui Min Toh, Jianbiao Zhou, Tze King Tan, Leilei Chen, Wee Joo Chng, Phaik Ju Teoh
Journal: Blood (2024)
The crossroads of clonal evolution, differentiation hierarchy and ontogeny in leukemia development
Authors: Christopher M. Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P. Papapetrou
Journal: Blood Cancer Discovery (2024)

Transformative technologies to sequence tumor genomes at large scale and single-cell resolution have exposed the repertoire of genetic alterations that are present in leukemia genomes, the timing of their acquisition and patterns of their co-occurrence. In parallel, single-cell multi-omics technologies are allowing us to map the differentiation paths and hierarchical structures of malignant cells and giving us a glimpse into hematopoietic development in prenatal life. We propose that interrogating how the genetic evolution, differentiation hierarchy and ontogeny of malignant myeloid cells intersect with each other, using new experimental systems and multimodal technologies, will fuel the next generation of research breakthroughs.
Clinical characteristics and serological profiles of Lyme disease in children: a 15-year retrospective cohort study in Switzerland
Authors: Beat M Greiter, Semjon Sidorov, Ester Osuna, Michelle Seiler, Christa Relly, Annette Hackenberg, Isabelle Luchsinger, Elvira Cannizzaro, Roland Martin, Martina Marchesi, Stefanie von Felten, Adrian Egli, Christoph Berger, Patrick M Meyer Sauteur
Journal: The Lancet Regional Health - Europe (2024)
Epidermal growth factor receptor and Ink4a/Arf: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis
Authors: Robert M. Bachoo, Elizabeth A. Maher, Keith L. Ligon, Norman E. Sharpless, Suzanne S. Chan, Mingjian James You, Yi Tang, Jessica DeFrances, Elizabeth Stover, Ralph Weissleder, David H. Rowitch, David N. Louis, Ronald A. DePinho
Journal: Cancer Cell (2024)
Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer
Authors: Inga-Maria Launonen, Iga Niemiec, María Hincapié-Otero, Erdogan Pekcan Erkan, Ada Junquera, Daria Afenteva, Matias M Falco, Zhihan Liang, Matilda Salko, Foteini Chamchougia, Angela Szabo, Fernando Perez-Villatoro, Yilin Li, Giulia Micoli, Ashwini Nagaraj, Ulla-Maija Haltia, Essi Kahelin, Jaana Oikkonen, Johanna Hynninen, Anni Virtanen, Ajit J Nirmal, Tuulia Vallius, Sampsa Hautaniemi, Peter K Sorger, Anna Vähärautio, Anniina Färkkilä
Journal: Cancer Cell (2024)
MR-Guided PET Reconstruction
Authors: Martin W. Huellner, Alexander Maurer, Matthew Spangler-Bickell
Journal: Clinical Nuclear Medicine (2024)

We report a case of a 33-year-old man with epilepsy and equivocal EEG, MRI signs of mesiotemporal sclerosis, and nondiagnostic standard FDG-PET imaging. The patient underwent repeat FDG-PET/MRI to clarify the sidedness of the epileptogenic focus and to confirm the suspected MTS. The standard PET reconstruction using block sequential regularized expectation maximization failed to provide evidence of a clear epileptogenic focus. However, using MR-guided PET reconstruction, circumscribed hypometabolism was observed in the right-sided entorhinal cortex, compatible with the epileptogenic focus. The MR-guided PET reconstruction provided significantly improved gray/white matter differentiation, enhancing confidence in imaging interpretation.
68Ga-DOTATATE PET/CT Demonstrated More Lesions of Leptomeningeal Metastases Compared With 123I-MIBG SPECT/CT in a Pediatric Neuroblastoma Patient
Authors: Lingling Zheng, Siqi Li, Yanfeng Xu, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 5-year-old girl with high-risk neuroblastoma after therapy was evaluated by 123 I-MIBG SPECT/CT and 68 Ga-DOTATATE PET/CT. Contrast-enhancement brain MRI demonstrated 2 metastatic lesions in the right parietal lobe of brain. One lesion showed abnormal MIBG accumulation associated with high density in the right central posterior gyrus, whereas the other lesion did not show MIBG uptake. In contrast, increased 68 Ga-DOTATATE uptake was seen in both lesions. Neuroblastoma cells were found by cytological examination of the cerebrospinal fluid.
Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma
Authors: Meletios A Dimopoulos, Peter M Voorhees, Fredrik Schjesvold, Yael C Cohen, Vania Hungria, Irwindeep Sandhu, Jindriska Lindsay, Ross I Baker, Kenshi Suzuki, Hiroshi Kosugi, Mark-David Levin, Meral Beksac, Keith Stockerl-Goldstein, Albert Oriol, Gabor Mikala, Gonzalo Garate, Koen Theunissen, Ivan Spicka, Anne K Mylin, Sara Bringhen, Katarina Uttervall, Bartosz Pula, Eva Medvedova, Andrew J Cowan, Philippe Moreau, Maria-Victoria Mateos, Hartmut Goldschmidt, Tahamtan Ahmadi, Linlin Sha, Annelore Cortoos, Eva G Katz, Els Rousseau, Liang Li, Robyn M Dennis, Robin Carson, S Vincent Rajkumar
Journal: New England Journal of Medicine (2024)

BackgroundDaratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved.MethodsIn this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria.ResultsAmong the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified.ConclusionsAmong patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.)
Advancing Cardiac Organoid Engineering Through Application of Biophysical Forces
Authors: Adriana Blazeski, Guillermo García-Cardeña, Roger D. Kamm
Journal: IEEE Reviews in Biomedical Engineering (2024)

Cardiac organoids represent an important bioengineering opportunity in the development of models to study human heart pathophysiology. By incorporating multiple cardiac cell types in three-dimensional culture and developmentally-guided biochemical signaling, cardiac organoids recapitulate numerous features of heart tissue. However, cardiac tissue also experiences a variety of mechanical forces as the heart develops and over the course of each contraction cycle. It is now clear that these forces impact cellular specification, phenotype, and function, and should be incorporated into the engineering of cardiac organoids in order to generate better models. In this review, we discuss strategies for engineering cardiac organoids and report the effects of organoid design on the function of cardiac cells. We then discuss the mechanical environment of the heart, including forces arising from tissue elasticity, contraction, blood flow, and stretch, and report on efforts to mimic these biophysical cues in cardiac organoids. Finally, we review emerging areas of cardiac organoid research, for the study of cardiac development, the formation of multi-organ models, and the simulation of the effects of spaceflight on cardiac tissue and consider how these investigations might benefit from the inclusion of mechanical cues.
Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial
Authors: Elias K. Mai, Uta Bertsch, Ema Pozek, Roland Fenk, Britta Besemer, Christine Hanoun, Roland Schroers, Ivana von Metzler, Mathias Hänel, Christoph Mann, Lisa B. Leypoldt, Bernhard Heilmeier, Stefanie Huhn, Sabine K. Vogel, Michael Hundemer, Christof Scheid, Igor W. Blau, Steffen Luntz, Niels Weinhold, Diana Tichy, Tobias A.W. Holderried, Karolin Trautmann-Grill, Deniz Gezer, Maika Klaiber-Hakimi, Martin Müller, Evgenii Shumilov, Wolfgang Knauf, Christian S. Michel, Thomas Geer, Hendrik Riesenberg, Christoph Lutz, Marc S. Raab, Axel Benner, Martin Hoffmann, Katja C. Weisel, Hans J. Salwender, Hartmut Goldschmidt, Miriam Ahlborn, Joachim Behringer, Helga Bernhard, Britta Besemer, Jörg Bittenbring, Igor Wolfgang Blau, Claus Bolling, Amelie Boquoi, Daniel Debatin, Gerlinde Egerer, Roland Fenk, Barbara Ferstl, Stefan Fronhoffs, Tobias Gaska, Thomas Geer, Deniz Gezer, Hartmut Goldschmidt, Martin Görner, Ullrich Graeven, Mathias Hänel, Bernhard Heilmeier, Michael Heinsch, Martin Hoffmann, Tobias A.W. Holderried, Olaf Hopfer, Snjezana Janjetovic, Maika Klaiber-Hakimi, Martine Klausmann, Stefan Klein, Wolfgang Knauf, Yon-Dschun Ko, Doris Maria Kraemer, Martin Kropff, Paul La Rosée, Rolf Mahlberg, Christoph Mann, Uwe Martens, Ivana von Metzler, Christian Michel, Martin Müller, Wolfram Pönisch, Peter Reimer, Claudia Riechel, Mark Ringhoffer, Mathias Rummel, Volker Runde, Hans Jürgen Salwender, Markus Schaich, Christoph Scheid, Martin Schmidt-Hieber, Daniel Schöndube, Roland Schroers, Hans-Joachim Schütte, Evgenii Shumilov, Peter Staib, Dirk Strumberg, Hans-Joachim Tischler, Karolin Trautmann-Grill, Walter Verbeek, Rudolf Weide, Eckhart Weidmann, Katja Weisel, Maike de Wit, Christiane Bernhardt, Thomas Fietz, Jochen Grassinger, Georg Köchling, Michael Neise, Stefan Schmitt, Heike Steiniger, Barbara Tschechne, Bettina Whitlock, Matthias Zaiß, Carsten Ziske
Journal: Journal of Clinical Oncology (2024)

Previously, addition of isatuximab (Isa) to standard-of-care lenalidomide-bortezomib-dexamethasone (RVd) in transplant-eligible patients with newly diagnosed multiple myeloma in the GMMG-HD7 trial (ClinicalTrials.gov identifier: NCT03617731) resulted in a significant increase of minimal residual disease negativity (MRD-) rates after induction therapy. A total of 662 patients were randomly assigned to receive induction therapy with Isa-RVd (n = 331) or RVd (n = 329), followed by single or tandem autologous stem-cell transplant and second random assignment to maintenance with lenalidomide alone or Isa-lenalidomide. We report updated results for part 1 from first random assignment to post-transplant. As of January 31, 2024, MRD- rates continued to deepen after transplant (66% Isa-RVd
Gain-of-Function Chromatin Remodeling Activity of Oncogenic FOXL2-C134W Reprograms Glucocorticoid Receptor Occupancy to Drive Granulosa Cell Tumors
Authors: Thomas Welte, Veena K. Vuttaradhi, Eleonora Y. Khlebus, Allison Brodsky, Alejandra Flores Legarreta, Joseph Celestino, Reid T. Powell, Clifford C. Stephan, Nghi Nguyen, Jian Li, Shiro Takamatsu, Katherine Calzoncinth, Anil K. Sood, David M. Gershenson, P. Andrew Futreal, Barrett Lawson, Robert Tyler. Hillman
Journal: Cancer Research (2024)

Adult type ovarian granulosa cell tumors (AGCTs) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a Forkhead box-family transcription factor important for ovarian function. Relapsed AGCT is incurable, but the mechanism of the unique FOXL2 mutation could confer therapeutic vulnerabilities. To identify FOXL2-C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2-C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific chromatin remodeling activity in FOXL2. FOXL2-C134W-dependent chromatin remodeling activity redirected glucocorticoid receptor chromatin occupancy to drive hyaluronan synthase 2 gene expression and increase extracellular hyaluronan secretion. Treatment of AGCT models with hyaluronidase reduced viability, and dexamethasone rescued this effect. Combinatorial drug-drug interaction experiments demonstrated that dexamethasone antagonizes the potency of paclitaxel, a chemotherapy agent frequently used in the treatment of AGCT. Thus, gain-of-function pioneering activity contributes to the oncogenic mechanism of FOXL2-C134W and creates a potentially targetable synergy with glucocorticoid signaling.
HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma
Authors: Rigney E. Turnham, Adriana Pitea, Gwendolyn M. Jang, Zhong Xu, Huat Chye Lim, Alex L. Choi, John Von Dollen, Rebecca S. Levin, James T. Webber, Elizabeth McCarthy, Junjie Hu, Xiaolei Li, Li Che, Ananya Singh, Alex Yoon, Gary Chan, Robin K. Kelley, Danielle L. Swaney, Wei Zhang, Sourav Bandyopadhyay, Fabian J. Theis, Manon Eckhardt, Xin Chen, Kevan M. Shokat, Trey Ideker, Nevan J. Krogan, John D. Gordan
Journal: Cancer Research (2024)

Hepatitis B virus (HBV) infections promote liver cancer initiation by inducing inflammation and cellular stress. Despite the primarily indirect effect on oncogenesis, HBV is associated with a recurrent genomic phenotype in HCC, suggesting that it impacts the biology of established HCC. Characterization of the interaction of HBV with host proteins and the mechanistic contributions of HBV to HCC initiation and maintenance could provide insights into HCC biology and uncover therapeutic vulnerabilities. Here, we used affinity purification mass spectrometry to comprehensively map a network of 145 physical interactions between HBV and human proteins in hepatocellular carcinoma (HCC). A subset of the host factors targeted by HBV proteins were preferentially mutated in non-HBV-associated HCC, suggesting that their interaction with HBV influences HCC biology. HBV interacted with proteins involved in mRNA splicing, mitogenic signaling, and DNA repair, with the latter set interacting with the HBV oncoprotein X (HBx). HBx remodeled the PP2A phosphatase complex by excluding striatin regulatory subunits from the PP2A holoenzyme, and the HBx effects on PP2A caused Hippo kinase activation. In parallel, HBx activated mTOR complex 2 (mTORC2), which can prevent YAP degradation. mTORC2-mediated upregulation of YAP was observed in human HCC specimens and mouse HCC models and could be targeted with mTOR kinase inhibitors. Thus, HBV interaction with host proteins rewires HCC signaling rather than directly activating mitogenic pathways, provide an alternative paradigm for the cellular effects of a tumor promoting virus.
Imlunestrant is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wildtype and Mutant Breast Cancer
Authors: Shripad V. Bhagwat, Cecilia Mur, Matthew Vandekopple, Baohui Zhao, Weihua Shen, Carlos Marugán, Andrew Capen, Lisa Kindler, Jennifer R. Stephens, Lysiane Huber, Mark A. Castanares, David Garcia-Tapia, Jeff D. Cohen, Jolie Bastian, Brian Mattioni, Eunice Yuen, Thomas K. Baker, Vivian Rodriguez Cruz, Dongling Fei, Jason R. Manro, Nicholas Pulliam, Michele S. Dowless, Maria Jesus. Ortiz Ruiz, Chunping Yu, Loredana Puca, Anke Klippel, Francesca Bacchion, Roohi Ismail-Khan, Vanessa Rodrik-Outmezguine, Sheng-Bin Peng, María Jose Lallena, Xueqian Gong, Alfonso de Dios
Journal: Cancer Research (2024)

Targeting of the estrogen receptor (ER) by anti-estrogens is the standard-of-care for patients with ER+ HER2- advanced/metastatic breast cancer. While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies. Here, we discovered and characterized imlunestrant, a next-generation potent, brain-penetrant oral selective estrogen receptor degrader (SERD). Imlunestrant degraded ERα and decreased ERα-mediated gene expression both in vitro and in vivo. Cell proliferation and tumor growth in ESR1 wildtype and mutant models were significantly inhibited by imlunestrant. Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared to vehicle or alternative SERD therapies. Together, these finding support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1 wildtype and mutant breast cancer, including brain metastatic tumors.
Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer
Authors: Luying Cui, Ruiqi Liu, Shuling Han, Chunhui Zhang, Bojun Wang, Yuli Ruan, Xuefan Yu, Yien Li, Yuanfei Yao, Xin Guan, Yuanyu Liao, Dan Su, Yue Ma, Shuijie Li, Chao Liu, Yanqiao Zhang
Journal: Cancer Research (2024)

Abstract ARID1A, a core constituent of SWI/SNF complex, is mutated in approximately 10% of colorectal cancers (CRC). While ARID1A deficiency corresponds to heightened immune activity in CRC, immune checkpoint inhibitors (ICIs) have shown limited efficacy in these tumors. The discovery of targetable vulnerabilities associated with ARID1A deficiency in CRC could expand treatment options for patients. In this study, we demonstrated that arachidonic acid metabolism inhibitors synergize with ICIs in ARID1A-deficient CRC by enhancing the activity of CD8+ T cells and inhibiting vasculogenic mimicry (VM). Epigenetic analysis using ATAC-seq and ChIP-qPCR revealed that the lack of ARID1A results in reduced levels of PTGS1 and PTGS2, the key enzymes that control the arachidonic acid pathway. Low PTGS1 and PTGS2 expression generated a reliance on the remaining functionality of the arachidonic acid pathway in ARID1A-deficient cells. The arachidonic acid pathway inhibitor aspirin selectively inhibited the growth of ARID1A-deficient CRC, and aspirin sensitized tumors lacking ARID1A to immunotherapy. Together, these findings suggest that blocking arachidonic acid metabolism can enhance immune responses against tumors by activating CD8+ T cells and inhibiting VM, which synergizes with ICIs to improve treatment of ARID1A-deficient CRC.
SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint that Enables Tumor Immune Evasion by Impairing T Cell Cytotoxicity
Authors: Hao Chi, Shouyan Deng, Ke Xu, Yibo Zhang, Teng Song, Jianghong Yu, Yiting Wang, Jiayang Liu, Yuan Zhang, Jiawei Shi, Yungang Wang, Jie Xu
Journal: Cancer Research (2024)

T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.