keyword
https://read.qxmd.com/read/38459027/structural-basis-for-self-discrimination-by-neoantigen-specific-tcrs
#1
JOURNAL ARTICLE
John P Finnigan, Jenna H Newman, Yury Patskovsky, Larysa Patskovska, Andrew S Ishizuka, Geoffrey M Lynn, Robert A Seder, Michelle Krogsgaard, Nina Bhardwaj
T cell receptors (TCR) are pivotal in mediating tumour cell cytolysis via recognition of mutation-derived tumour neoantigens (neoAgs) presented by major histocompatibility class-I (MHC-I). Understanding the factors governing the emergence of neoAg from somatic mutations is a major focus of current research. However, the structural and cellular determinants controlling TCR recognition of neoAgs remain poorly understood. This study describes the multi-level analysis of a model neoAg from the B16F10 murine melanoma, H2-Db /Hsf2 p...
March 8, 2024: Nature Communications
https://read.qxmd.com/read/38242983/author-correction-gemcitabine-and-cisplatin-plus-nivolumab-as-organ-sparing-treatment-for-muscle-invasive-bladder-cancer-a-phase-2-trial
#2
Matthew D Galsky, Siamak Daneshmand, Sudeh Izadmehr, Edgar Gonzalez-Kozlova, Kevin G Chan, Sara Lewis, Bassam El Achkar, Tanya B Dorff, Jeremy Paul Cetnar, Brock O Neil, Anishka D'Souza, Ronac Mamtani, Christos Kyriakopoulos, Tomi Jun, Mahalya Gogerly-Moragoda, Rachel Brody, Hui Xie, Kai Nie, Geoffrey Kelly, Amir Horowitz, Yayoi Kinoshita, Ethan Ellis, Yohei Nose, Giorgio Ioannou, Rafael Cabal, Diane M Del Valle, G Kenneth Haines, Li Wang, Kent W Mouw, Robert M Samstein, Reza Mehrazin, Nina Bhardwaj, Menggang Yu, Qianqian Zhao, Seunghee Kim-Schulze, Robert Sebra, Jun Zhu, Sacha Gnjatic, John Sfakianos, Sumanta K Pal
No abstract text is available yet for this article.
January 19, 2024: Nature Medicine
https://read.qxmd.com/read/38241440/a-synthetic-agent-ameliorates-polycystic-kidney-disease-by-promoting-apoptosis-of-cystic-cells-through-increased-oxidative-stress
#3
JOURNAL ARTICLE
Bogdan I Fedeles, Rishi Bhardwaj, Yasunobu Ishikawa, Sakunchai Khumsubdee, Matteus Krappitz, Nina Gubina, Isabel Volpe, Denise C Andrade, Parisa Westergerling, Tobias Staudner, Jake Campolo, Sally S Liu, Ke Dong, Yiqiang Cai, Michael Rehman, Anna-Rachel Gallagher, Somsak Ruchirawat, Robert G Croy, John M Essigmann, Sorin V Fedeles, Stefan Somlo
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic kidney disease and the fourth leading cause of end-stage kidney disease, accounting for over 50% of prevalent cases requiring renal replacement therapy. There is a pressing need for improved therapy for ADPKD. Recent insights into the pathophysiology of ADPKD revealed that cyst cells undergo metabolic changes that up-regulate aerobic glycolysis in lieu of mitochondrial respiration for energy production, a process that ostensibly fuels their increased proliferation...
January 23, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37783966/gemcitabine-and-cisplatin-plus-nivolumab-as-organ-sparing-treatment-for-muscle-invasive-bladder-cancer-a-phase-2-trial
#4
JOURNAL ARTICLE
Matthew D Galsky, Siamak Daneshmand, Sudeh Izadmehr, Edgar Gonzalez-Kozlova, Kevin G Chan, Sara Lewis, Bassam El Achkar, Tanya B Dorff, Jeremy Paul Cetnar, Brock O Neil, Anishka D'Souza, Ronac Mamtani, Christos Kyriakopoulos, Tomi Jun, Mahalya Gogerly-Moragoda, Rachel Brody, Hui Xie, Kai Nie, Geoffrey Kelly, Amir Horwitz, Yayoi Kinoshita, Ethan Ellis, Yohei Nose, Giorgio Ioannou, Rafael Cabal, G Kenneth Haines, Li Wang, Kent W Mouw, Robert M Samstein, Reza Mehrazin, Nina Bhardwaj, Menggang Yu, Qianqian Zhao, Seunghee Kim-Schulze, Robert Sebra, Jun Zhu, Sacha Gnjatic, John Sfakianos, Sumanta K Pal
Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy...
October 2, 2023: Nature Medicine
https://read.qxmd.com/read/37684128/genitourinary-cancer-neoadjuvant-therapies-current-and-future-approaches
#5
REVIEW
Sujit S Nair, Dimple Chakravarty, Vaibhav Patel, Nina Bhardwaj, Ashutosh K Tewari
Neoadjuvant therapies can improve tolerability, reduce tumor volume to facilitate surgery, and assess subsequent treatment response. Therefore, there is much enthusiasm for expanding the benefits of cancer therapies to the neoadjuvant setting to reduce recurrence and improve survival in patients with localized or locally advanced genitourinary (GU) cancer. This approach is clinically pertinent because these treatments are administered primarily to treatment-naive patients and can elicit the greatest drug response...
December 2023: Trends in Cancer
https://read.qxmd.com/read/37607770/antitumor-immunity-as-the-basis-for-durable-disease-free-treatment-free-survival-in-patients-with-metastatic-urothelial-cancer
#6
JOURNAL ARTICLE
Jonathan Anker, Sumanta K Pal, Seunghee Kim-Schulze, Huan Wang, Rebecca Halperin, Andrew Uzilov, Naoko Imai, Shingo Eikawa, Takuro Saito, Robert Sebra, Noah M Hahn, Manishkumar Patel, Jingjing Qi, Hui Xie, Nina Bhardwaj, Sacha Gnjatic, Matthew D Galsky
Cisplatin-based chemotherapy has been associated with durable disease control in a small subset of patients with metastatic urothelial cancer. However, the mechanistic basis for this phenomenon has remained elusive. Antitumor immunity may underlie these exceptional responders. In a phase II trial evaluating a phased schedule of gemcitabine and cisplatin followed by gemcitabine and cisplatin with ipilimumab for metastatic urothelial cancer, 4 of 36 patients achieved durable disease-free treatment-free survival (DDFTFS) and remain in remission over 5 years after enrolment on the study...
August 2023: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/37492581/immune-escape-and-resistance-to-immunotherapy-in-mismatch-repair-deficient-tumors
#7
REVIEW
Guillaume Mestrallet, Matthew Brown, Cansu Cimen Bozkus, Nina Bhardwaj
Up to 30% of colorectal, endometrial and gastric cancers have a deficiency in mismatch repair (MMR) protein expression due to either germline or epigenetic inactivation. Patients with Lynch Syndrome who inherit an inactive MMR allele have an up to 80% risk for developing a mismatch repair deficient (MMRd) cancer. Due to an inability to repair DNA, MMRd tumors present with genomic instability in microsatellite regions (MS). Tumors with high MS instability (MSI-H) are characterized by an increased frequency of insertion/deletions (indels) that can encode novel neoantigens if they occur in coding regions...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37438891/pediatric-aerodigestive-medicine-advancing-collaborative-care-for-children-with-oropharyngeal-dysphagia
#8
JOURNAL ARTICLE
Amornluck Krasaelap, Daniel R Duncan, Ramy M M Sabe, Vrinda Bhardwaj, Diana G Lerner, Benjamin D Gold, Richard Paul Boesch, Christophe Faure, Daniel von Allmen, Dana Williams, Eric Chiou, Emily DeBoer, Erik Hysinger, Jennifer Maybee, Julie Khlevner, Kara Larson, Kimberly Morris, Lauren Jalali, Maireade McSweeney, Matthew T Brigger, Melanie Greifer, Michael Rutter, Nina Williams, Ram Kumar Subramanyan, Matthew J Ryan, Sari Acra, Scott Pentiuk, Joel Friedlander, Steven E Sobol, Ajay Kaul, Lev Dorfman, Anil Darbari, Jeremy D Prager, Rachel Rosen, Jose T Cocjin, Hayat Mousa
OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders...
July 13, 2023: Journal of Pediatric Gastroenterology and Nutrition
https://read.qxmd.com/read/37363104/updates-on-radiotherapy-immunotherapy-combinations-proceedings-of-6-th-annual-immunorad-conference
#9
REVIEW
Fabiana Gregucci, Sheila Spada, Mary Helen Barcellos-Hoff, Nina Bhardwaj, Charleen Chan Wah Hak, Alba Fiorentino, Chandan Guha, Monica L Guzman, Kevin Harrington, Fernanda G Herrera, Jamie Honeychurch, Theodore Hong, Lorea Iturri, Elisabeth Jaffee, Sana D Karam, Simon R V Knott, Constantinos Koumenis, David Lyden, Ariel E Marciscano, Alan Melcher, Michele Mondini, Anna Mondino, Zachary S Morris, Sean Pitroda, Sergio A Quezada, Laura Santambrogio, Stephen Shiao, John Stagg, Irma Telarovic, Robert Timmerman, Marie-Catherine Vozenin, Ralph Weichselbaum, James Welsh, Anna Wilkins, Chris Xu, Roberta Zappasodi, Weiping Zou, Alexandre Bobard, Sandra Demaria, Lorenzo Galluzzi, Eric Deutsch, Silvia C Formenti
Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels...
2023: Oncoimmunology
https://read.qxmd.com/read/37315532/cancer-immunity-derailed-pge-2-misconducts-cdc1s
#10
COMMENT
Matthew Brown, Michelle A Tran, Nina Bhardwaj
Type 1 conventional dendritic cells (cDC1s) are critical for CD8+ T cell-mediated tumor control. In this issue of Immunity, Bayerl et al.1 expose a mechanism leading to cancer progression where prostaglandin E2 induces dysfunctional cDC1s, which cannot coordinate CD8+ T cell migration and expansion.
June 13, 2023: Immunity
https://read.qxmd.com/read/37081148/trem2-macrophages-drive-nk-cell-paucity-and-dysfunction-in-lung-cancer
#11
JOURNAL ARTICLE
Matthew D Park, Ivan Reyes-Torres, Jessica LeBerichel, Pauline Hamon, Nelson M LaMarche, Samarth Hegde, Meriem Belabed, Leanna Troncoso, John A Grout, Assaf Magen, Etienne Humblin, Achuth Nair, Martina Molgora, Jinchao Hou, Jenna H Newman, Adam M Farkas, Andrew M Leader, Travis Dawson, Darwin D'Souza, Steven Hamel, Alfonso Rodriguez Sanchez-Paulete, Barbara Maier, Nina Bhardwaj, Jerome C Martin, Alice O Kamphorst, Ephraim Kenigsberg, Maria Casanova-Acebes, Amir Horowitz, Brian D Brown, Lucas Ferrari De Andrade, Marco Colonna, Thomas U Marron, Miriam Merad
Natural killer (NK) cells are commonly reduced in human tumors, enabling many to evade surveillance. Here, we sought to identify cues that alter NK cell activity in tumors. We found that, in human lung cancer, the presence of NK cells inversely correlated with that of monocyte-derived macrophages (mo-macs). In a murine model of lung adenocarcinoma, we show that engulfment of tumor debris by mo-macs triggers a pro-tumorigenic program governed by triggering receptor expressed on myeloid cells 2 (TREM2). Genetic deletion of Trem2 rescued NK cell accumulation and enabled an NK cell-mediated regression of lung tumors...
May 2023: Nature Immunology
https://read.qxmd.com/read/36778273/structural-basis-for-self-discrimination-by-neoantigen-specific-tcrs
#12
John Finnigan, Jenna Newman, Yury Patskovsky, Larysa Patskovska, Andrew Ishizuka, Geoffrey Lynn, Robert Seder, Michelle Krogsgaard, Nina Bhardwaj
Physical interactions between T cell receptors (TCRs) and mutation-derived tumour neoantigens (neoAg) presented by major histocompatibility class-I (MHC-I) enable sensitive and specific cytolysis of tumour cells. Adoptive transfer of neoAg-reactive T cells in patients is correlated with response to immunotherapy; however, the structural and cellular mechanisms of neoAg recognition remain poorly understood. We have identified multiple cognate neoAg:TCRs from B16F10, a common murine implantable tumour model of melanoma...
January 31, 2023: Research Square
https://read.qxmd.com/read/36275666/strategies-to-overcome-dc-dysregulation-in-the-tumor-microenvironment
#13
REVIEW
Guillaume Mestrallet, Kazuki Sone, Nina Bhardwaj
Dendritic cells (DCs) play a key role to modulate anti-cancer immunity in the tumor microenvironment (TME). They link innate to adaptive immunity by processing and presenting tumor antigens to T cells thereby initiating an anti-tumor response. However, subsets of DCs also induce immune-tolerance, leading to tumor immune escape. In this regard, the TME plays a major role in adversely affecting DC function. Better understanding of DC impairment mechanisms in the TME will lead to more efficient DC-targeting immunotherapy...
2022: Frontiers in Immunology
https://read.qxmd.com/read/36129800/tumor-infiltrating-myeloid-cells-confer-de-novo-resistance-to-pd-l1-blockade-through-emt-stromal-and-tgf-beta-dependent-mechanisms
#14
JOURNAL ARTICLE
Haocheng Yu, John P Sfakianos, Li Wang, Yang Hu, Jorge Daza, Matthew D Galsky, Harkirat S Sandhu, Olivier Elemento, Bishoy M Faltas, Adam M Farkas, Nina Bhardwaj, Jun Zhu, David J Mulholland
Most bladder cancers are poorly responsive to immune checkpoint blockade (ICB). With the need to define mechanisms of de novo resistance, including contributions from the tumor microenvironment (TME), we used single-cell transcriptional profiling to map tumor infiltrating lymphocytic and myeloid cells in 10 human bladder tumors obtained from patients with a history of smoking either with or without previous ICB. Human data sets were qualitatively compared with single cell data sets from the BBN carcinogen induced mouse model of bladder cancer which was poorly responsive to PD-L1 blockade...
September 21, 2022: Molecular Cancer Therapeutics
https://read.qxmd.com/read/36099881/nkg2a-and-hla-e-define-an-alternative-immune-checkpoint-axis-in-bladder-cancer
#15
JOURNAL ARTICLE
Bérengère Salomé, John P Sfakianos, Daniel Ranti, Jorge Daza, Christine Bieber, Andrew Charap, Christian Hammer, Romain Banchereau, Adam M Farkas, Dan Fu Ruan, Sudeh Izadmehr, Daniel Geanon, Geoffrey Kelly, Ronaldo M de Real, Brian Lee, Kristin G Beaumont, Sanjana Shroff, Yuanshuo A Wang, Ying-Chih Wang, Tin Htwe Thin, Monica Garcia-Barros, Everardo Hegewisch-Solloa, Emily M Mace, Li Wang, Timothy O'Donnell, Diego Chowell, Ruben Fernandez-Rodriguez, Mihaela Skobe, Nicole Taylor, Seunghee Kim-Schulze, Robert P Sebra, Doug Palmer, Eleanor Clancy-Thompson, Scott Hammond, Alice O Kamphorst, Karl-Johan Malmberg, Emanuela Marcenaro, Pedro Romero, Rachel Brody, Mathias Viard, Yuko Yuki, Maureen Martin, Mary Carrington, Reza Mehrazin, Peter Wiklund, Ira Mellman, Sanjeev Mariathasan, Jun Zhu, Matthew D Galsky, Nina Bhardwaj, Amir Horowitz
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms...
September 12, 2022: Cancer Cell
https://read.qxmd.com/read/35907399/dark-genome-bright-ideas-recent-approaches-to-harness-transposable-elements-in-immunotherapies
#16
REVIEW
Ashley Reid Cahn, Nina Bhardwaj, Nicolas Vabret
Transposable elements (TEs), which make up almost half of the human genome, often display altered expression in cancers. Here, we review recent progress in elucidating the role of TEs as mediators of immune responses in cancer and discuss how novel therapeutic strategies can harness TE immunogenicity for cancer immunotherapy.
August 8, 2022: Cancer Cell
https://read.qxmd.com/read/35851878/author-correction-neoadjuvant-clinical-trials-provide-a-window-of-opportunity-for-cancer-drug-discovery
#17
Thomas U Marron, Matthew D Galsky, Bachir Taouli, Maria Isabel Fiel, Stephen Ward, Edward Kim, David Yankelevitz, Deborah Doroshow, Emma Guttman-Yassky, Benjamin Ungar, Saurabh Mehandru, Benjamin J Golas, Daniel Labow, John Sfakianos, Sujit S Nair, Dimple Chakravarty, Michael Buckstein, Xiaoyu Song, Effi Kenigsberg, Sacha Gnjatic, Brian D Brown, Joseph Sparano, Ashutosh Tewari, Myron Schwartz, Nina Bhardwaj, Miriam Merad
No abstract text is available yet for this article.
August 2022: Nature Medicine
https://read.qxmd.com/read/35789859/y-rnas-are-conserved-endogenous-rig-i-ligands-across-rna-virus-infection-and-are-targeted-by-hiv-1
#18
JOURNAL ARTICLE
Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Ramya Gopal, Christopher McClain, Petr Šulc, Sreekumar Balan, Yannis Rahou, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y Sanchez David, Lise Chauveau, Nolwenn Jouvenet, Martin Markowitz, Sylvie van der Werf, Olivier Schwartz, Frédéric Tangy, Nina Bhardwaj, Benjamin D Greenbaum, Anastassia V Komarova
Pattern recognition receptors (PRRs) protect against microbial invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. Although microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation remains overlooked. Here, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors (RLRs) upon infection by different RNA viruses. In each infection, several RNAs transcribed by RNA polymerase III (Pol3) specifically engaged RLRs, particularly the family of Y RNAs...
July 15, 2022: IScience
https://read.qxmd.com/read/35704596/calreticulin-mutant-myeloproliferative-neoplasms-induce-mhc-i-skewing-which-can-be-overcome-by-an-optimized-peptide-cancer-vaccine
#19
JOURNAL ARTICLE
Mathieu Gigoux, Morten O Holmström, Roberta Zappasodi, Joseph J Park, Stephane Pourpe, Cansu Cimen Bozkus, Levi M B Mangarin, David Redmond, Svena Verma, Sara Schad, Mariam M George, Divya Venkatesh, Arnab Ghosh, David Hoyos, Zaki Molvi, Baransel Kamaz, Anna E Marneth, William Duke, Matthew J Leventhal, Max Jan, Vincent T Ho, Gabriela S Hobbs, Trine Alma Knudsen, Vibe Skov, Lasse Kjær, Thomas Stauffer Larsen, Dennis Lund Hansen, R Coleman Lindsley, Hans Hasselbalch, Jacob H Grauslund, Thomas L Lisle, Özcan Met, Patrick Wilkinson, Benjamin Greenbaum, Manuel A Sepulveda, Timothy Chan, Raajit Rampal, Mads H Andersen, Omar Abdel-Wahab, Nina Bhardwaj, Jedd D Wolchok, Ann Mullally, Taha Merghoub
The majority of JAK2V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting in a common carboxyl-terminal mutant fragment (CALRMUT ), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALRMUT -specific T cells are rare in patients with CALRMUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALRMUT MPN from two independent cohorts...
June 15, 2022: Science Translational Medicine
https://read.qxmd.com/read/35681714/association-between-incidental-pelvic-inflammation-and-aggressive-prostate-cancer
#20
JOURNAL ARTICLE
Dimple Chakravarty, Parita Ratnani, Li Huang, Zachary Dovey, Stanislaw Sobotka, Roy Berryhill, Harri Merisaari, Majd Al Shaarani, Richa Rai, Ivan Jambor, Kamlesh K Yadav, Sandeep Mittan, Sneha Parekh, Julia Kodysh, Vinayak Wagaskar, Rachel Brody, Carlos Cordon-Cardo, Dmitry Rykunov, Boris Reva, Elai Davicioni, Peter Wiklund, Nina Bhardwaj, Sujit S Nair, Ashutosh K Tewari
The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) &gt; 2 and ≥ pT3 stage, at resection...
May 31, 2022: Cancers
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