tbuckley/cabot-search huggingface dataset:
Early detection of pancreatic cancer by a high-throughput protease-activated nanosensor assay
Authors: Jose L. Montoya Mira, Arnaud Quentel, Ranish K. Patel, Dove Keith, Megan Sousa, Jessica Minnier, Benjamin R. Kingston, Larry David, Sadik C. Esener, Rosalie C. Sears, Charles D. Lopez, Brett C. Sheppard, Utkan Demirci, Melissa H. Wong, Jared M. Fischer
Journal: Science Translational Medicine (2025)

Pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-related death. Patients are frequently diagnosed in the more advanced stages when effective treatment options are limited; however, earlier detection of PDAC by liquid biopsy may expand treatment options and improve survival outcomes. Here, we developed a noninvasive detection assay for PDAC based on serum protease activity to leverage the increase in cancer-associated protease activity in the peripheral blood of patients with PDAC. We screened a series of protease-cleavable peptide probes for the discrimination of PDAC samples versus healthy controls and noncancerous pancreatic disease. We identified a single MMP-sensitive probe, which could distinguish PDAC from controls with 79 ± 6% accuracy. We further developed this probe into a rapid magnetic nanosensor assay, termed PAC-MANN, that measures serum protease cleavage of a target-probe nanosensor with a simple fluorescent readout. In a longitudinal cohort of patients undergoing surgical removal of the primary tumor, the probe cleavage signal was reduced by 16 ± 24% after surgery. In a separate blinded retrospective study, the PAC-MANN assay identified PDAC samples with 98% specificity and 73% sensitivity across all stages and distinguished 100% of patients with noncancer pancreatic disease relative to patients with PDAC. The PAC-MANN assay combined with the clinical biomarker CA 19-9 was 85% sensitive for detection of stage I PDAC with 96% specificity. Therefore, the PAC-MANN assay is a rapid, high-throughput method that uses small blood volumes with the potential to enhance early PDAC detection, specifically among individuals at high risk of developing PDAC.
In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene
Authors: Marco De Giorgi, So Hyun Park, Adam Castoreno, Mingming Cao, Ayrea Hurley, Lavanya Saxena, Marcel A. Chuecos, Christopher J. Walkey, Alexandria M. Doerfler, Mia N. Furgurson, M. Cecilia Ljungberg, Kalyani R. Patel, Sarah Hyde, Tyler Chickering, Stephanie Lefebvre, Kelly Wassarman, Patrick Miller, June Qin, Mark K. Schlegel, Ivan Zlatev, Jun Han, Christine Beeton, Rich Gang Li, Jong Kim, James F. Martin, Karl-Dimiter Bissig, Vasant Jadhav, Gang Bao, William R. Lagor
Journal: Science Translational Medicine (2025)

Homology-directed repair (HDR)–based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested Repair Drive, a platform technology for selectively expanding HDR-corrected hepatocytes in adult mice in vivo. Repair Drive involves transient conditioning of the liver by knocking down an essential gene, fumarylacetoacetate hydrolase ( Fah ), and delivering an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive increased the percentage of correctly targeted hepatocytes in healthy wild-type mice up to 25%, which resulted in a fivefold increased expression of a therapeutic transgene, human factor IX ( FIX ). Repair Drive was well tolerated and did not induce toxicity or tumorigenesis during a 1-year follow-up. This approach may broaden the range of liver diseases that can be treated with somatic genome editing.
Antisense oligonucleotide–mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington’s disease iPSC–derived striatal neurons
Authors: Emma L. Bunting, Jasmine Donaldson, Sarah A. Cumming, Jessica Olive, Elizabeth Broom, Mihai Miclăuș, Joseph Hamilton, Matthew Tegtmeyer, Hien T. Zhao, Jonathan Brenton, Won-Seok Lee, Robert E. Handsaker, Susan Li, Brittany Ford, Mina Ryten, Steven A. McCarroll, Holly B. Kordasiewicz, Darren G. Monckton, Gabriel Balmus, Michael Flower, Sarah J. Tabrizi
Journal: Science Translational Medicine (2025)

Expanded CAG alleles in the huntingtin ( HTT ) gene that cause the neurodegenerative disorder Huntington’s disease (HD) are genetically unstable and continue to expand somatically throughout life, driving HD onset and progression. MSH3, a DNA mismatch repair protein, modifies HD onset and progression by driving this somatic CAG repeat expansion process. MSH3 is relatively tolerant of loss-of-function variation in humans, making it a potential therapeutic target. Here, we show that an MSH3 -targeting antisense oligonucleotide (ASO) effectively engaged with its RNA target in induced pluripotent stem cell (iPSC)–derived striatal neurons obtained from a patient with HD carrying 125 HTT CAG repeats (the 125 CAG iPSC line). ASO treatment led to a dose-dependent reduction of MSH3 and subsequent stalling of CAG repeat expansion in these striatal neurons. Bulk RNA sequencing revealed a safe profile for MSH3 reduction, even when reduced by &gt;95%. Maximal knockdown of MSH3 also effectively slowed CAG repeat expansion in striatal neurons with an otherwise accelerated expansion rate, derived from the 125 CAG iPSC line where FAN1 was knocked out by CRISPR-Cas9 editing. Last, we created a knock-in mouse model expressing the human MSH3 gene and demonstrated effective in vivo reduction in human MSH3 after ASO treatment. Our study shows that ASO-mediated MSH3 reduction can prevent HTT CAG repeat expansion in HD 125 CAG iPSC–derived striatal neurons, highlighting the therapeutic potential of this approach.
Predicting patent challenges for small-molecule drugs: A cross-sectional study
Authors: Ally Memedovich, Brian Steele, Taylor Orr, Shanzeh Chaudhry, Mina Tadrous, Aaron S. Kesselheim, Aidan Hollis, Reed F. Beall
Journal: PLoS Medicine (2025)

Background The high cost of prescription drugs in the United States is maintained by brand-name manufacturers’ competition-free period made possible in part through patent protection, which generic competitors must challenge to enter the market early. Understanding the predictors of these challenges can inform policy development to encourage timely generic competition. Identifying categories of drugs systematically overlooked by challengers, such as those with low market size, highlights gaps where unchecked patent quality and high prices persist, and can help design policy interventions to help promote timely patient access to generic drugs including enhanced patent scrutiny or incentives for challenges. Our objective was to characterize and assess the extent to which market size and other drug characteristics can predict patent challenges for brand-name drugs. Methods and findings This cross-sectional study included new patented small-molecule drugs approved by the FDA from 2007 to 2018. Market size, patent, and patent challenge data came from IQVIA MIDAS pharmaceutical quarterly sales data, the FDA’s Orange Book database, and the FDA’s Paragraph IV list. Predictive models were constructed using elastic net and random forest classification. The primary outcome was the occurrence of a patent challenge within the first year of eligibility. Of the 210 new small-molecule drugs included in the sample, 55% experienced initiation of patent challenge within the first year of eligibility. Market value was the most important predictor variable, with larger markets being more likely to be associated with patent challenges. Drugs in the anti-infective therapeutic class or those with fast-track approval were less likely to be challenged. The limitations of this work arise from the exclusion of variables that were not readily available publicly, will be the target of future research, or were deemed beyond the scope of this project. Conclusions Generic competition does not occur with the same timeliness across all drug markets, which can leave granted patents of questionable merit in place and sustain high brand-name drug prices. Predictive models may help direct limited resources for post-grant patent validity review and adjust policy when generic competition is lacking.
Global burden of HBV-related liver disease: Primary liver cancer due to chronic HBV infection increased in over one-third of countries globally from 2000 to 2021
Authors: Pojsakorn Danpanichkul, Kwanjit Duangsonk, Vincent L. Chen, Preenapun Saokhieo, Disatorn Dejvajara, Banthoon Sukphutanan, Majd B. Aboona, Chawin Lopimpisuth, Yanfang Pang, Andrew F. Ibrahim, Michael B. Fallon, Daniel Q. Huang, Donghee Kim, Amit G. Singal, Ju Dong Yang, Bashar A. Aqel, Norah A. Terrault, Karn Wijarnpreecha
Journal: Hepatology (2025)

Backgrounds &amp;Aims: Hepatitis B virus (HBV)-related liver disease ranks as the seventh leading cause of mortality. Despite advances in prevention and treatment, global disparities in the burden of primary liver cancer (PLC) persist. We evaluate global trends in the prevalence, incidence, and death of HBV-related liver disease. Approach and Results: Data from the Global Burden of Disease Study 2021 evaluated acute HBV infection, HBV-related cirrhosis, and HBV-related liver cancer prevalence, incidence, and death. In 2021, there were 7.30 million cases of acute HBV, 283.64 million cases of HBV-related cirrhosis, and 288,110 cases of HBV-related PLC. HBV-related PLC accounted for 39% of the global incidence of PLC; Western Pacific had the highest rates for HBV-related PLC, with an incidence of 5.24 and a death rate of 4.38 per 100,000 population. Between 2000-2021, age-standardized incidence, prevalence, and death rates from HBV-related liver disease decreased; however, the incidence of HBV-related PLC rose in 65 countries from 2000 to 2021. In parallel, age-standardized prevalent rates from HBV-related PLC increased in Europe (Annual percent change [APC]: 0.77%, 95% confidence interval [CI] 0.72 to 0.81%) and the Americas (APC: 1.05%, 95%CI 1.00 to 1.10%). Conclusion: From 2000 to 2021, decreases in HBV-related liver disease incidence and prevalence were observed; however, more than one-third of countries showed an increase in the incidence of HBV-related PLC. These findings highlight the need for strengthened HBV treatment efforts to reduce the risk of liver cancer.
Outcomes Among Adult Recipients of CAR T-cell Therapy for Burkitt Lymphoma
Authors: Laura Samples, Hossein Sadrzadeh, Matthew J. Frigault, Caron A. Jacobson, Mehdi Hamadani, Ashwath Gurumurthi, Paolo Strati, Roni Shouval, Ariela Noy, Peter A Riedell, Saurabh Dahiya, David G Maloney, Brian G Till, Alexandre V. Hirayama, Jordan Gauthier, Ajay K Gopal, Stephen D Smith, Christina Poh, Ryan C Lynch, Chaitra Ujjani, Mengyang Di, Vikram Raghunathan, Mehrdad Shakib-Azar, Kikkeri N Naresh, Ted A Gooley, Jean A. Yared, Michael D Jain, Frederick L Locke, Lori A. Leslie, Narendranath Epperla, Monalisa Ghosh, Alan P Skarbnik, Brian T. Hill, Manali Kamdar, Valentín Ortiz-Maldonado, Nuria Martínez-Cibrian, Leyla Shune, Mazyar Shadman
Journal: Blood (2025)
Evaluation of FeMnN alloy bioresorbable flow diverting stents in the rabbit abdominal aorta
Authors: Alexander A Oliver, Cem Bilgin, Mitchell L Connon, Andrew J Vercnocke, Esref A Bayraktar, Jonathan Cortese, Daying Dai, Yong Hong Ding, Sarah A Erdahl, John Pederson, Kent D Carlson, Adam J Griebel, Jeremy E Schaffer, Dan Dragomir-Daescu, Ramanathan Kadirvel, Roger J Guillory, David F Kallmes
Journal: Bioactive Materials (2025)
Polymer-modified DNA hydrogels for living mitochondria and nanozyme delivery in the treatment of rheumatoid arthritis
Authors: Fuxiao Wang, Yafei Han, Qirong Zhou, Shihao Sheng, Yan Hu, Hao Zhang, Xiao Chen, Chongru He, Hongbo Tan, Long Bai, Jiacan Su
Journal: Bioactive Materials (2025)
CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma
Authors: Simon J. Harrison, Cyrille Touzeau, Nicolas Kint, Katherine Li, Tamia Nguyen, Caroline Mayeur-Rousse, Marzia Rahman, Yannick Le Bris, Jeremy Er, Juliette Eugene-Lamer, Nicole M. Haynes, Jessica Li, Rebecca C. Abbott, Caroline Bodet-Milin, Anne Moreau, Eric Letouzé, Nikoletta Lendvai, Jordan M. Schecter, William Deraedt, Arnob Banerjee, Tamar Lengil, Martin Vogel, Brad Foulk, Hao Zhao, Denis Smirnov, Ana Slaughter, Carolina Lonardi, Erin Lee, Loreta Marquez, Ayah Sankari, Vicki Plaks, Jose Octavio Costa Filho, Nitin Patel, Dong Geng, Thomas Gastinne, Hannah Kelly, Ing Soo Tiong, Marion Eveillard, Patrice Chevallier, Stephen Lade, Philippe Moreau, Sean Grimmond, Jane Oliaro, Benoit Tessoulin, Piers Blombery
Journal: New England Journal of Medicine (2025)

We describe two patients in whom malignant monoclonal T-cell lymphoproliferation developed after administration of chimeric antigen receptor (CAR) T-cell therapy with ciltacabtagene autoleucel (cilta-cel) in the phase 3 CARTITUDE-4 trial. Monoclonal T cells from both patients had detectable CAR transgene expression and integration. The clinicogenomic features of these CAR transgenic T-cell lymphoproliferative neoplasms suggest that multiple potential intrinsic or extrinsic factors (or both) contributed to their pathogenesis, such as transduction of preexisting TET2-mutated T cells, followed by acquisition of further oncogenic genomic variants. Other potential contributors include germline genomic variation, viral infections, and previous treatment for myeloma. In the absence of direct evidence, the contribution of insertional mutagenesis to the development of T-cell lymphoma is currently unclear. (Funded by Johnson & Johnson and Legend Biotech USA; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).
Maternal Anti-PF4 Antibodies as Cause of Neonatal Stroke
Authors: Silke Häusler, Linda Schönborn, Johann Gradl, Janne Cadamuro, Katja Steinbrücker, Marta Broto, Marta Palicio, Kathrin Budde, Jan Wesche, Andreas Greinacher, Thomas Thiele
Journal: New England Journal of Medicine (2025)
Pulse Oximetry and Skin Tone in Children
Authors: Joseph R Starnes, Wendi Welch, Christopher C Henderson, Stephen Hudson, Scott Risney, George T Nicholson, Thomas P Doyle, Dana R Janssen, Bevan P Londergan, David A Parra, James C Slaughter, Muktar H Aliyu, John A Graves, Jonathan H Soslow
Journal: New England Journal of Medicine (2025)

Simultaneous measurements in children revealed overestimation of arterial saturation by pulse oximetry that was attributable to spectrophotometric measures of skin tone.
Three-year follow-up analysis of first-line axicabtagene ciloleucel in high-risk large B-cell lymphoma (ZUMA-12)
Authors: Julio C. Chavez, Michael Dickinson, Javier Munoz, Matthew L. Ulrickson, Catherine Thieblemont, Olalekan O. Oluwole, Alex F. Herrera, Chaitra Ujjani, Yi Lin, Peter A. Riedell, Natasha Kekre, Sven de Vos, Jacob Wullf, Chad M. Williams, Joshua Winters, Ioana Magdalena Kloos, Hairong Xu, Sattva S. Neelapu
Journal: Blood (2025)

ZUMA-12 is a multicenter phase 2 study that evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in patients with high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n=37; 15.9 months median follow-up), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, followed by lymphodepleting chemotherapy and a single axi-cel infusion of 2×106 CAR T cells/kg. Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n=37) increased after the primary analysis to 86% (95% CI, 71-95), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival in response-evaluable patients were 81.8% (63.9-91.4), 73.0% (55.6-84.4), 75.1% (57.5-86.2), and 81.1% (64.4-90.5), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis, none were related to axi-cel. Eight patients died on study, 2 of whom died from non-relapse mortality causes. After ≥3 years of follow-up, axi-cel demonstrated a high cure rate in first-line high-risk LBCL, with no new safety signals after the primary analysis. Further assessments are needed to determine its benefit versus first-line standard-of-care. This trial was registered at clinicaltrials.gov, as #NCT03761056.
Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother–infant pairs (MTN-043): a phase 3B, open-label, randomised trial
Authors: Lisa M Noguchi, Maxensia Owor, Nyaradzo M Mgodi, Brenda Gati Mirembe, Sufia Dadabhai, Elizea Horne, Holly Gundacker, Barbra A Richardson, Katherine Bunge, Rachel Scheckter, Mei Song, Mark A Marzinke, Peter L Anderson, Edward Livant, Cindy Jacobson, Jeanna M Piper, Nahida Chakhtoura, Sharon L Hillier, Jennifer E Balkus
Journal: The Lancet HIV (2025)
Efficacy and effectiveness of therapist-guided internet versus face-to-face cognitive behavioural therapy for depression via counterfactual inference using naturalistic registers and machine learning in Finland: a retrospective cohort study
Authors: Tom H Rosenström, Suoma E Saarni, Samuli I Saarni, Jaakko Tammilehto, Jan-Henry Stenberg
Journal: The Lancet Psychiatry (2025)
Inflammatory bowel disease in south Asia: a scoping review
Authors: Shabari Shenoy, Anuraag Jena, Carrie Levinson, Vishal Sharma, Parakkal Deepak, Tina Aswani-Omprakash, Shaji Sebastian, Jean-Frederic Colombel, Manasi Agrawal
Journal: The Lancet. Gastroenterology & hepatology (2025)
The causal association between polyunsaturated fatty acids and acne: A two-sample Mendelian randomization study
Authors: Bo Ri Kim, Gahyun Kim, Seon-Pil Jin, Chong Won Choi, Jinho Kim, Hyunsun Park
Journal: British Journal of Dermatology (2025)

Abstract Background Observational studies have demonstrated a close association between polyunsaturated fatty acids (PUFAs) and acne. However, the findings of clinical trials have been inconsistent, leaving the causal relationship between PUFAs and acne unclear. Objectives To investigate the causal association between genetically proxied PUFAs and acne risk Methods Mendelian randomization (MR) was performed using single-nucleotide polymorphisms associated with PUFAs as instrumental variables. The causal associations between PUFAs and acne were estimated among 115,006 UK biobank participants and 363,927 participants of Finnish descent. Results Genetically predicted docosahexaenoic acid (DHA) levels (Beta= -0.303; 95% CI: –0.480 to –0.126; p = 7.74E-04) and its percentage to total fatty acids (Beta= -0.402; 95% CI: –0.651 to –0.258; p = 5.91E-06) showed a significant causal association with a decreased risk of acne. Conversely, genetically predicted percentages of linoleic acid (LA) in total fatty acids (Beta=0.768; 95% CI: 0.411–0.126; p = 2.87E-04) and omega-6: omega-3 (Beta=0.373; 95% CI: 0.142–0.604; p = 4.48E-03) were robustly associated with an increased risk of acne. These effects were attenuated after excluding a genetic variant of rs174528 located upstream of fatty acid desaturase 1 (FADS1), highlighting the biological link between FADS1 and delta-5 desaturase activity. Multivariable MR analysis indicated that PUFAs were causally associated with acne, independent of body mass index. Conclusions Our study indicates that high DHA levels and their ratios to total fatty acids have causal protective effects against acne, while high LA levels and omega-6: omega-3 ratio are associated with increased acne risk. This association was largely attributable to the influence of genetic variants related to FADS1.
Hepatic endoplasmic reticulum-derived nanodiscs for broad-spectrum drug detoxification
Authors: Lei Sun, Kailin Feng, Dean Bai, Yiyan Yu, Wei-Ting Shen, Jiayuan Alex Zhang, Ronnie H Fang, Weiwei Gao, Liangfang Zhang
Journal: Biomaterials (2025)

Drug overdose is a pressing global public health challenge, with current detoxification treatments often lacking the broad-spectrum efficacy needed for emergency applications. Inspired by the unique advantages of cell membrane-derived nanodiscs (CNDs), including their compact size, rapid distribution, and preservation of native cell membrane functions, we developed endoplasmic reticulum (ER)-derived nanodiscs (ER-NDs) from the ER membranes of mouse hepatic cells for broad-spectrum drug detoxification. ER-NDs retain natural cytochrome P450 (CYP) enzymes, enabling effective detoxification of three model drugs: bupropion, haloperidol, and propranolol. Cell-based assays demonstrated ER-NDs' ability to mitigate drug-induced cytotoxicity, reduce oxidative stress, and restore antioxidant defenses. In mouse models of drug intoxication, ER-ND treatment significantly improved survival rates and alleviated drug-induced oxidative damage. Importantly, ER-NDs showed no evidence of acute toxicity in vivo. These findings underscore the potential of ER-NDs as a versatile platform for broad-spectrum drug detoxification and as a promising tool for managing drug intoxication in emergency and clinical settings.
Diagnostic accuracy of the Scandinavian guidelines for minor and moderate head trauma in children: a prospective, pragmatic, validation study
Authors: Fredrik Wickbom, Rakel Bremell, Sarah Thornberg, Jorge Sotoca Fernandez, Beatrice Magnusson, Rasmus Silfver, Aqeel Chaudhry, Kristoffer Kjellröier, Hanna Farahnoosh Afsan, Marcus Bergman, Amel Jumppanen, Malin Johansson, Sascha Östberg, Christian Kamis, Mihai Ölund, Emma Jeppsson, Albert Modin, Anders Santoft, Lovisa Borg, Cathrine Gatzinsky, Maria Lönn, Olga Calcagnile, Ramona Astrand, Terje Sundstrøm, Niklas Marklund, Johan Undén
Journal: The Lancet Regional Health - Europe (2025)
Synergistic restoration of spinal cord injury through hyaluronic acid conjugated hydrogel-polydopamine nanoparticles combined with human mesenchymal stem cell transplantation
Authors: Yanbing Kao, Wei Song, Renjie Zhang, Guangjin Gu, Heping Qiu, Wenyuan Shen, Hanming Zhu, Yanchun Liu, Yu Yang, Haoyun Liu, Zhihao Zhang, Xiaohong Kong, Shiqing Feng
Journal: Bioactive Materials (2025)
γδ T-cell autoresponses to ectopic membrane proteins: a new type of pattern recognition
Authors: Hongqin You, Xiangjin Zhang, Hui Chen, Chang Liu, Da Teng, Jiajia Han, Ming Chen, Yongsheng Pang, Jianmin Zhang, Menghua Cai, Yueqi Zhao, Qingqing Dong, Shuli Wang, Yi Xu, Yu Hu, Peng Dong, Wei He
Journal: Cellular and Molecular Immunology (2025)

Abstract T-cell receptor (TCR) γδ-expressing cells are conserved lymphocytes of innate immunity involved in first-line defense and immune surveillance. TCRγδ recognizes protein/nonprotein ligands without the help of the major histocompatibility complex (MHC), especially via direct binding to protein ligands, which is dependent primarily on the δ chain complementary determining region 3 (CDR3δ). However, the mechanism of protein‒antigen recognition by human γδ TCRs remains poorly defined. We hypothesize that γδ TCRs recognize self-proteins expressed ectopically on the cell membrane that are derived from intracellular components under stress. Here, we mapped 16 intercellular self-proteins among 21,000 proteins with a huProteinChip as putative ligands for Vδ1/Vδ2 TCRs, 13 for Vδ1 TCRs and 3 for Vδ2 TCRs. Functional tests confirmed that ectopic nucleolin (NCL) is a ligand for the Vδ1 TCR, whereas protein-glutamine γ-glutamyltransferase K (TGM1) is a ligand for the Vδ2 TCR. In the context of radiation exposure, the ectopic expression of intracellular proteins on the tumor cell surface is related to the increased antitumor cytotoxicity of γδ T cells both in vitro and in vivo. In conclusion, the recognition of intracellular proteins that are ectopically expressed on somatic cells by human γδ TCRs is a basic interaction mechanism that enables new types of immune pattern recognition and a novel γδ TCR-ligand-based strategy for tumor immunotherapy.