tbuckley/cabot-search huggingface dataset:
β3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity
Authors: Joseph M. Valentine, Maryam Ahmadian, Omer Keinan, Mohammad Abu-Odeh, Peng Zhao, Xin Zhou, Mark P. Keller, Hui Gao, Ruth T. Yu, Christopher Liddle, Michael Downes, Jin Zhang, Aldons J. Lusis, Alan D. Attie, Ronald M. Evans, Mikael Rydén, Alan R. Saltiel
Journal: Journal of Clinical Investigation (2021)

The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.
THE COST OF INADEQUATE BOWEL PREPARATION
Authors: J. Cudmore, N. Zhang, J. Taylor, C.L. Murphy
Journal: Endoscopy (2022)

Aims Adequate bowel preparation is essential for successful, high-quality colonoscopy. Inadequate preparation for colonoscopy can necessitate repeat procedures or alternative investigations such as CT colonography. Inpatient status is one of a number of factors associated with poor preparation.
An imidazole modified lipid confers enhanced mRNA-LNP stability and strong immunization properties in mice and non-human primates
Authors: Manon Ripoll, Marie-Clotilde Bernard, Céline Vaure, Emilie Bazin, Sylvie Commandeur, Vladimir Perkov, Katia Lemdani, Marie-Claire Nicolaï, Patrick Bonifassi, Antoine Kichler, Benoit Frisch, Jean Haensler
Journal: Biomaterials (2022)

The mRNA vaccine technology has promising applications to fight infectious diseases as demonstrated by the licensing of two mRNA-based vaccines, Comirnaty® (Pfizer/BioNtech) and Spikevax® (Moderna), in the context of the Covid-19 crisis. Safe and effective delivery systems are essential to the performance of these vaccines and lipid nanoparticles (LNPs) able to entrap, protect and deliver the mRNA in vivo are considered by many as the current "best in class". Nevertheless, current mRNA/LNP vaccine technology has still some limitations, one of them being thermostability, as evidenced by the ultracold distribution chain required for the licensed vaccines. We found that the thermostability of mRNA/LNP, could be improved by a novel imidazole modified lipid, DOG-IM4, in combination with standard helper lipids. DOG-IM4 comprises an ionizable head group consisting of imidazole, a dioleoyl lipid tail and a short flexible polyoxyethylene spacer between the head and tail. Here we describe the synthesis of DOG-IM4 and show that DOG-IM4 LNPs confer strong immunization properties to influenza HA mRNA in mice and macaques and a remarkable stability to the encapsulated mRNA when stored liquid in phosphate buffered saline at 4 °C. We speculate the increased stability to result from some specific attributes of the lipid's imidazole head group.
Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of <i>FAM19A4/miR124-2</i> DNA Methylation (CONCERVE Study)
Authors: Wieke W. Kremer, Stèfanie Dick, Daniëlle A.M. Heideman, Renske D.M. Steenbergen, Maaike C.G. Bleeker, Harold R. Verhoeve, W. Marchien van Baal, Nienke van Trommel, Gemma G. Kenter, Chris J.L.M. Meijer, Johannes Berkhof
Journal: Journal of Clinical Oncology (2022)

Cervical screening can prevent cancer by detection and treatment of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Screening also results in considerable overtreatment because many CIN2/3 lesions show spontaneous regression when left untreated. In this multicenter longitudinal cohort study of women with untreated CIN2/3, the prognostic value of FAM19A4/miR124-2 methylation was evaluated for clinical regression.Women with CIN2/3 were prospectively followed for 24 months. Surgical excision was replaced by a wait-and-see policy. FAM19A4/miR124-2 methylation was evaluated on all clinician-collected samples and self-collected samples collected at baseline. Every 6 months, human papillomavirus (HPV) testing and cytology were conducted on a clinician-collected sample, and a colposcopic examination was performed by a gynecologist to exclude progression. At the final study visit, two biopsies were taken. Clinical regression was defined as histologically confirmed absence of CIN2+ or an HPV-negative clinician-collected sample with normal cytology. Regression incidences were estimated using the Kaplan-Meier method.One hundred fourteen women (median age, 30 years; range, 20-53 years) were included, 80 of whom were diagnosed with CIN2 and 34 with CIN3. During the study, 65.8% of women (75/114) did not receive surgical treatment. Women with a negative FAM19A4/miR124-2 result on the baseline clinician-collected sample showed more clinical regression (74.7%) than women with a positive methylation result (51.4%, P = .013). Regression in women with a negative FAM19A4/miR124-2 methylation test was highest when cytology was atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (88.4%) or HPV16 was negative (85.1%).Most women with untreated CIN2/3 and a negative baseline FAM19A4/miR124-2 methylation test showed clinical regression. Methylation, in combination with cytology or HPV genotyping, can be used to support a wait-and-see policy in women with CIN2/3.
EFFICACY OF VERY LOW-VOLUME BOWEL PREPARATION FOR COLONOSCOPY: LESS IS MORE!
Authors: G.F. Bonura, G. Impellizzeri, T. Gabbani, J. Rainer, A. Curatolo, L. Ottaviani, S. Deiana, P. Biancheri, P. Soriani, M. Manno
Journal: Endoscopy (2022)

Aims Bowel cleansing quality is a key performance indicator for colonoscopy. In our study, we compared polyethylene glycol (PEG)-based bowel preparations (BPs) in terms of bowel cleansing quality, cecal intubation rate and patient compliance.
ELDERLY VS. YOUNG PATIENTS : CLINICAL, ENDOSCOPIC AND PROGNOSTIC PARTICULARITIES IN CASE OF UPPER GASTROINTESTINAL HEMORRHAGE : PROSPECTIVE STUDY
Authors: A. Touibi, A. Benhamdane, T. Addajou, A. Sair, S. Rokhsi, S. Mrabti, R. Berraida, I. El Koti, F. Rouibaa, A. Benkirane, H. Seddik
Journal: Endoscopy (2022)

Aims The aim of our study is to compare the epidemiological, clinical, endoscopic, therapeutic and prognostic characteristics of UDH in young vs. elderly subjects.
NEEDLE-KNIFE SPHINCTEROTOMY AS A PRECUT PROCEDURE IN PATIENTS WITH NON-DILATED BILIARY TRACT: TECHNICAL SUCCESS RATE AND COMPLICATION RATE
Authors: V. Busto, A. Arrubla, I. Rodríguez, N. Hervás, S. Bravo, M. Ganuza, V. Jusué, J. Carrascosa, M. Gómez, B. González de la Higuera, J.J. Vila
Journal: Endoscopy (2022)

Aims Needle-knife sphincterotomy as a precut procedure (PS) in patients with non-dilated bile duct carries an increased risk of complications. Working hypothesis: A targeted PS with identification of the papillary submucosal common bile duct does not imply a greater risk of complications.
KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming
Authors: Xiao-Dan Ma, Shui-Dan Xu, Shi-Hui Hao, Kai Han, Jie-Wei Chen, Han Ling, Ri-Xin Chen, Xiao-Han Jin, Jing-Hua Cao, Jin-Long Lin, Qing-Jian Ou, Yu-Jing Fang, Zhi-Zhong Pan, Dan Xie, Feng-Wei Wang
Journal: Molecular Therapy (2022)

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.
86P Change in dietary habits does not affect body composition in early breast cancer patients treated with aromatase inhibitor
Authors: L. Laini, A. Bonalumi, S. Bosio, N. Villa, V. Amoroso, L. Lorini, B. Zanini, G. Schivardi, P. Di Mauro, D. Cosentini, L. Vassalli, A. Alberti, A. Esposito, V. Cremaschi, E.L. Simoncini, A. Berruti, R. Pedersini
Journal: Annals of Oncology (2022)
Derivation and Validation of a Score for Predicting Poor Neurocognitive Outcomes in Acute Carbon Monoxide Poisoning
Authors: Sung Hwa Kim, Yoonsuk Lee, Soo Kang, Jin Hui Paik, Hyun Kim, Yong Sung Cha
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Preventing neurocognitive sequelae is a major goal of treating acute carbon monoxide (co) poisoning. There is a lack of reliable score systems exist for assessing the probability of these sequelae. <h3>Objective</h3> To develop and validate a novel clinical scoring system for predicting poor neurocognitive outcomes after acutecopoisoning. <h3>Design, Setting, and Participants</h3> This prognostic study included derivation and validation cohorts based on consecutive patient data prospectively collected at university hospitals from January 2006 to July 2021 in Wonju, Republic of Korea, and from August 2016 to June 2020 in Incheon, Republic of Korea. Participants included individuals aged 16 years or older admitted withcopoisoning. Data were analyzed from October 2021 to January 2022. <h3>Exposures</h3> Clinical and laboratory variables. <h3>Main Outcomes and Measures</h3> The outcome of interest was neurocognitive sequelae at 4 weeks aftercopoisoning. Logistic regression models were used to identify predictors of poor neurocognitive outcomes in the derivation cohort. Outcomes were assessed using the Global Deterioration Scale [GDS] at 1-month aftercoexposure and classified as good (1-3 points) or poor (4-7 points). <h3>Results</h3> A total of 1282 patients (median [IQR] age, 47.0 [35.0-59.0] years; 810 [63.2%] men) were assessed, including 1016 patients in the derivation cohort and 266 patients in the validation cohort. The derivation cohort included 126 patients (12.4%) with poor GDS scores. Among 879 patients in the derivation cohort with 1-year follow-up data, 757 (86.1%) had unchanged GDS scores, 102 (11.6%) had improved GDS scores, and 20 (2.3%) had worsened GDS scores. In the final prediction model, age older than 50 years (1 point), Glasgow Coma Scale score of 12 or less (1 point), shock (1 point), serum creatine kinase level greater than 320 U/L at emergency department presentation (1 point), and no use of hyperbaric oxygen therapy (1 point) remained factors significantly associated with worse outcome; therefore, this scoring system was called<i>COGAS</i>(creatine kinase, hyperbaric oxygen therapy, Glasgow Coma Scale, age, shock). Area under the receiver operating characteristic curve for COGAS score was 0.862 (95% CI, 0.828-0.895) for the derivation cohort and 0.870 (95% CI, 0.779-0.961) for the validation cohort. <h3>Conclusions and Relevance</h3> These findings suggest that assessing the COGAS score during the early phase ofcopoisoning may help identify patients at risk of poor neurocognitive sequelae.
164O Health-related quality of life (HRQoL) with pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as 1L treatment for advanced triple-negative breast cancer (TNBC): Results from KEYNOTE-355
Authors: D.W. Cescon, P. Schmid, H.S. Rugo, S-A. Im, M. Md Yusof, C.E. Gallardo, O. Lipatov, C.H. Barrios, J.M. Perez Garcia, H. Iwata, N. Masuda, M.A. Torregroza Otero, E. Gokmen, S. Loi, A. Haiderali, X. Zhou, Z. Guo, A. Martin Nguyen, J. Cortés
Journal: Annals of Oncology (2022)
183P Efficacy and safety of tenalisib, a PI3K δ/γ and SIK3 inhibitor in patients with locally advanced or metastatic breast cancer: Initial results from a phase II study
Authors: T. Makharadze, I.Z. Kiladze, G. Dzagnidze, N. Semionova-Peskova, L. Katselashvili, N. Vekua, K. Routhu, P. Barde, A. Nair
Journal: Annals of Oncology (2022)
Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies
Authors: Sisi Zheng, Elisabeth Gillespie, Ammar S. Naqvi, Katharina E. Hayer, Zhiwei Ang, Manuel Torres-Diz, Mathieu Quesnel-Vallières, David A. Hottman, Asen Bagashev, John Chukinas, Carolin Schmidt, Mukta Asnani, Rawan Shraim, Deanne M. Taylor, Susan R. Rheingold, Maureen M. O'Brien, Nathan Singh, Kristen W. Lynch, Marco Ruella, Yoseph Barash, Sarah K. Tasian, Andrei Thomas-Tikhonenko
Journal: Blood Cancer Discovery (2021)

Downregulation of surface epitopes causes postimmunotherapy relapses in B-lymphoblastic leukemia (B-ALL). Here we demonstrate that mRNA encoding CD22 undergoes aberrant splicing in B-ALL. We describe the plasma membrane-bound CD22 Δex5-6 splice isoform, which is resistant to chimeric antigen receptor (CAR) T cells targeting the third immunoglobulin-like domain of CD22. We also describe splice variants skipping the AUG-containing exon 2 and failing to produce any identifiable protein, thereby defining an event that is rate limiting for epitope presentation. Indeed, forcing exon 2 skipping with morpholino oligonucleotides reduced CD22 protein expression and conferred resistance to the CD22-directed antibody-drug conjugate inotuzumab ozogamicin in vitro. Furthermore, among inotuzumab-treated pediatric patients with B-ALL, we identified one nonresponder in whose leukemic blasts Δex2 isoforms comprised the majority of CD22 transcripts. In a second patient, a sharp reduction in CD22 protein levels during relapse was driven entirely by increased CD22 exon 2 skipping. Thus, dysregulated CD22 splicing is a major mechanism of epitope downregulation and ensuing resistance to immunotherapy.
ERCP IN A PATIENT WITH ROUX-EN-Y HEPATOJEJUNOSTOMY STENOSIS SUCCESSFULLY MANAGED BY ARGON PLASMA COAGULATION AND DILATION
Authors: J. Espinel, E. Pinedo, M. Jiménez, P. Suarez
Journal: Endoscopy (2022)

A 46 year-old-woman with Roux-en-Y hepaticojejunostomy (HJ) after iatrogenic bile duct injury during a cholecystectomy 10 years ago, was admitted for cholangitis. An MRCP showed a stenosis of the HJ anastomosis. An ERCP was carried out using an SB enteroscope with a distal cap. Then, we could see a very narrow right-HJ stenosis that just allowed a 0.035 guidewire to pass through, which prevented the passage of the dilator catheter. Thus, we applied APC in the stenosis which allowed to pass through the dilation catheter. We dilated the stenosis with a 8 mm balloon catheter. No complications happened.
CONTRIBUTION OF DIGESTIVE ENDOSCOPY IN CASE OF DIGESTIVE THICKENING ON IMAGING
Authors: A. Hassine, S. Mrabet, I. Akkari, E. Ben Jazia
Journal: Endoscopy (2022)

Aims The recent advent of new imaging techniques has certainly changed the management of DigestiveTract pathologies. The aim of our study was to assess the benefit of digestive endoscopy in patients with digestive thickening on imaging.
Safety and immunogenicity of CoronaVac in people living with HIV: a prospective cohort study
Authors: Lucas C Netto, Karim Y Ibrahim, Camila M Picone, Ana Paula P S Alves, Eliane V Aniceto, Mariana R Santiago, Patrícia S S Parmejani, Nadia E Aikawa, Ana C Medeiros-Ribeiro, Sandra G Pasoto, Emily F N Yuki, Carla G S Saad, Tatiana Pedrosa, Amanda N Lara, Carina Ceneviva, Eloisa Bonfa, Esper G Kallas, Vivian I Avelino-Silva
Journal: The Lancet HIV (2022)
ENDOSCOPIC SLEEVE GASTROPLASTY USING THE ENDOMINA DEVICE AS A BRIDGE-TO SURGERY PROCEDURE FOR SUPEROBESE PATIENTS
Authors: F. Prinz, K. Gröhl, A. Ebigbo, E. Schnoy, H. Messmann, S.K. Goelder, S. Nagl
Journal: Endoscopy (2022)

Aims Endoscopic sleeve gastroplasty (ESG) is a minimally invasive bariatric procedure that reduces the gastric volume and delays gastric emptying to facilitate weight loss. The effectiveness and safety of ESG in weight loss has mainly been described for patients with class I and II obesity, but not routinely for superobese and high-risk patients. This study aims to evaluate the safety, feasibility, and efficacy of ESG for superobese and high-risk patients as a bridge to surgery (BTS) procedure.
SLOUGHING ESOPHAGUS
Authors: S. Dogan, F. Omurca, E. Firat, A. Farooq
Journal: Endoscopy (2022)

Esophagus dissecans superficialis is rarew endoscopy findings, it is chracterized by sloughing off esophagus mucosa. it has been linked conditions such as eosinophilic esophaitis , lichen planus, pemphigus vulgaris.
PRSS1 HEREDITARY CHRONIC PANCREATITIS: ERCP WITH PANCREATOSCOPY AND PANCREATIC LITHOTRIPSY
Authors: F. Cravero, M. Gesualdo, M. Sacco, F. Rizzi, E. Dall'Amico, M.T. Staiano, C.G. De Angelis
Journal: Endoscopy (2022)

36 year old man with PRSS1 hereditary pancreatitis complaining severe abdominal pain and presenting dilated main pancreatic duct with a big stone (14 mm) at genu. Pain control was achieved by pancreatic drainage with plastic stent. The next year pancreatic stent was meant to be replaced, but stent went broken and retained during extraction. Our goal was pancreatic stone fragmentation and drainage, retained pancreatic stent removal and insertion of new pancreatic stent. Peroral pancreatoscopy was performed using cholangioscope on guidewire during ERCP. The big stone was fragmented with electrohydraulic lithotripsy device and finally impacted stent could be removed.
GASTROSCOPY REFERRALS IN PRIMARY CARE MEET APPROPRIATE CRITERIA IN ONLY HALF OF REFERRALS
Authors: L.M. Koggel, M.A. Lantinga, F.L. Büchner, J.P.H. Drenth, J. Frankema, E. Heeregrave, M. Heringa, M.E. Numans, P.D. Siersema
Journal: Endoscopy (2022)

Aims Annually, high numbers of diagnostic gastroscopies are performed. It has been suggested that up to 40% of gastroscopy referrals by general practitioners (GPs) do not meet referral criteria. In this study, we evaluated the appropriateness of gastroscopy referrals by GPs in daily clinical practice.
EVALUATION OF ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION AND FINE NEEDLE BIOPSY IN SOLID PANCREATIC NEOPLASM IN LOW VOLUME HOSPITAL
Authors: G. Aguero Garcete, A. Masi Miranda, J. Ferreira Duarte, C. Caballero Llano
Journal: Endoscopy (2022)

Aims In recent years new technology has been introduced in needles to improve tissue acquisition and thus ameliorate the diagnostic yield in pancreatic neoplasms. This improvement may be more important in less experienced endosonographer. We performed a retrospective study to determine the difference in diagnostic yield between 22 G Fine-Needle Aspiration (FNA) and 22 G Fine-Needle biopsies (with the Franseen tip needle) (FNB) in the study of solid tumours of the pancreas.
EVALUATION OF LIVER FAT AND FIBROSIS WITH FIBROSCAN IN CELIAC PATIENTS
Authors: K. Nuriyev, Z. İstemihan, İ.V. Şenkal, Z. İmanov, B. Çavuş, A. Çifçibaşı Örmeci, F. Akyüz, K. Demir, F. Beşışık, S. Kaymakoğlu
Journal: Endoscopy (2022)

Aims The aim of this study is to determine the fibrosis and adiposity scores with Fibroscan, a noninvasive method in celiac patients,and to determine the factors affecting them.
DEVELOPMENT AND VALIDATION OF THE GLOBAL POLYPECTOMY ASSESSMENT TOOL (GPAT) – A NOVEL ONLINE ASSESSMENT TOOL FOR ANY COLORECTAL POLYPECTOMY
Authors: A.C.P. De Crem, L. Debels, C. Schoonjans, L. Desomer, J. Anderson, R. Valori, D.J. Tate
Journal: Endoscopy (2022)

Aims Colorectal polypectomy is commonly incomplete with high variability between endoscopists resulting in interval cancer or repeated procedures. Existing scores for polypectomy technique are cumbersome and difficult to use. We developed a user-friendly online assessment tool for any colorectal polypectomy: the Global Polypectomy Assessment Tool (GPAT). We aimed to validate GPAT with endoscopists of varied experience.
UPPER GASTROINTESTINAL BLEEDING: A PROSPECTIVE EPIDEMIOLOGICAL STUDY OF 72 CASES
Authors: L. Nkurunziza, H. El Bacha, S. Mechhor, T. Gharbi, N. Benzzoubeir, I. Errabih
Journal: Endoscopy (2022)

Aims Upper gastrointestinal bleeding (UGIB) is a common medical condition that results in substantial morbidity and mortality.
COMBINED FORWARD AND RETROFLEXION WITHDRAWAL DURING COLONOSCOPY USING A SECOND-GENERATION SHORT-TURN RADIUS COLONOSCOPE
Authors: C. Robles-Medranda, C. Cifuentes-Gordillo, M. Puga-Tejada, J. Alcivar-Vasquez, R. Del Valle, H. Alvarado, M. Egas-Izquierdo, M. Arevalo-Mora, R.C. Merfea, J. Barreto Perez, J. Rodriguez, H.P. Lukashok
Journal: Endoscopy (2022)

Aims Polyps and adenomas are missed indivertibly in colonoscopy due to factors such as the location of lesions on difficult areas (i.e., proximal side of ileocecal valve). We aimed to evaluate the impact of combined forward and retroflexion withdrawal using a second-generation short-turn radius colonoscope during colonoscopy.
NKG2A and PD-L1 expression panel predicts clinical benefits from adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer
Authors: Sen Yan, Han Zeng, Kaifeng Jin, Fei Shao, Zhaopei Liu, Yuan Chang, Yiwei Wang, Yu Zhu, Zewei Wang, Le Xu, Jiejie Xu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Programmed cell death ligand-1 (PD-L1) expression as a single biomarker for immune checkpoint blockade (ICB) was controversial. NKG2A was a PD1/PD-L1 axis-related immunity-dependent factor. NKG2A and PD-L1 expression as a combinatorial biomarker might improve the prediction of PD-L1 in patients with muscle-invasive bladder cancer (MIBC).Three independent cohorts were enrolled in our study. 195 patients with bladder-derived metastatic urothelial carcinoma on PD-L1 inhibitor treatment from the IMvigor210 trial were enrolled. 124 MIBC patients from Zhongshan Hospital and 391 patients with MIBC from The Cancer Genome Atlas database were included in this study.The PD-L1/NKG2A-based risk stratification was validated in three independent cohorts, and its association with response to ICB and adjuvant chemotherapy (ACT), immune contexture and molecular features was evaluated. Histologic staining and genomic algorithm were performed to detect characteristics of NKG2A and PD-L1 expression and infiltration of immune cells.We identified NKG2AhiPD-L1hi patients could benefit more from cisplatin-based ACT and PD-L1 inhibitor. Further analyses revealed NKG2A and PD-L1 expression panel was linked to an immune-active tumor microenvironment with highly immune effector cells and effector molecules. In addition, NKG2A and PD-L1 expression panel was intrinsically correlated with genomic alterations related to therapeutic response in MIBC.NKG2A and PD-L1 expression panel was associated with an immune inflamed microenvironment and acted as a combinatorial biomarker to predict the therapeutic response to ACT and PD-L1 blockade in MIBC.