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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) > 2 and ≥ pT3 stage, at resection...
May 31, 2022: Cancers
#22
JOURNAL ARTICLE
Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st-2nd, 2021.
Paolo A Ascierto, Antonio Avallone, Nina Bhardwaj, Carlo Bifulco, Sergio Bracarda, Joshua D Brody, Luigi Buonaguro, Sandra Demaria, Leisha A Emens, Robert L Ferris, Jérôme Galon, Samir N Khleif, Christopher A Klebanoff, Tamara Laskowski, Ignacio Melero, Chrystal M Paulos, Sandro Pignata, Marco Ruella, Inge Marie Svane, Janis M Taube, Bernard A Fox, Patrick Hwu, Igor Puzanov
Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These include inhibitors of additional immune checkpoints, adoptive cell transfer (ACT), and therapeutic vaccines. Patients with advanced cancers who previously had limited treatment options available may now benefit from immunotherapies that can offer durable responses and improved survival outcomes...
June 7, 2022: Journal of Translational Medicine
#23
JOURNAL ARTICLE
Thomas U Marron, Matthew D Galsky, Bachir Taouli, Maria Isabel Fiel, Stephen Ward, Edward Kim, David Yankelevitz, Deborah Doroshow, Emma Guttman, 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.
March 28, 2022: Nature Medicine
#24
JOURNAL ARTICLE
Thomas U Marron, Maria Isabel Fiel, Pauline Hamon, Nathalie Fiaschi, Edward Kim, Stephen C Ward, Zhen Zhao, Joel Kim, Paul Kennedy, Ganesh Gunasekaran, Parissa Tabrizian, Deborah Doroshow, Meredith Legg, Ashley Hammad, Assaf Magen, Alice O Kamphorst, Muhammed Shareef, Namita T Gupta, Raquel Deering, Wei Wang, Fang Wang, Pradeep Thanigaimani, Jayakumar Mani, Leanna Troncoso, Alexandra Tabachnikova, Christie Chang, Guray Akturk, Mark Buckup, Steven Hamel, Giorgio Ioannou, Clotilde Hennequin, Hajra Jamal, Haley Brown, Antoinette Bonaccorso, Daniel Labow, Umut Sarpel, Talia Rosenbloom, Max W Sung, Baijun Kou, Siyu Li, Vladimir Jankovic, Nicola James, Sara C Hamon, Hung Kam Cheung, Jennifer S Sims, Elizabeth Miller, Nina Bhardwaj, Gavin Thurston, Israel Lowy, Sacha Gnjatic, Bachir Taouli, Myron E Schwartz, Miriam Merad
BACKGROUND: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma...
March 2022: Lancet. Gastroenterology & Hepatology
#25
JOURNAL ARTICLE
Evan Greene, Greg Finak, Leonard A D'Amico, Nina Bhardwaj, Candice D Church, Chihiro Morishima, Nirasha Ramchurren, Janis M Taube, Paul T Nghiem, Martin A Cheever, Steven P Fling, Raphael Gottardo
We introduce a new method for single-cell cytometry studies, FAUST, which performs unbiased cell population discovery and annotation. FAUST processes experimental data on a per-sample basis and returns biologically interpretable cell phenotypes, making it well suited for the analysis of complex datasets. We provide simulation studies that compare FAUST with existing methodology, exemplifying its strength. We apply FAUST to data from a Merkel cell carcinoma anti-PD-1 trial and discover pre-treatment effector memory T cell correlates of outcome co-expressing PD-1, HLA-DR, and CD28...
December 10, 2021: Patterns
#26
REVIEW
Christian Rolfo, Noy Meshulami, Alessandro Russo, Florian Krammer, Adolfo García-Sastre, Philip C Mack, Jorge E Gomez, Nina Bhardwaj, Amin Benyounes, Rafael Sirera, Amy Moore, Nicholas Rohs, Claudia I Henschke, David Yankelevitz, Jennifer King, Yu Shyr, Paul A Bunn, John D Minna, Fred R Hirsch
Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management...
November 10, 2021: Journal of Thoracic Oncology
#27
JOURNAL ARTICLE
Olivera J Finn, Nina Bhardwaj, Steven P Fling, Judith C Kaiser
No abstract text is available yet for this article.
October 13, 2021: Cancer Immunology Research
#28
REVIEW
Vladimir Roudko, Cansu Cimen Bozkus, Benjamin Greenbaum, Aimee Lucas, Robert Samstein, Nina Bhardwaj
Defective DNA mismatch repair (dMMR) is associated with many cancer types including colon, gastric, endometrial, ovarian, hepatobiliary tract, urinary tract, brain and skin cancers. Lynch syndrome - a hereditary cause of dMMR - confers increased lifetime risk of malignancy in different organs and tissues. These Lynch syndrome pathogenic alleles are widely present in humans at a 1:320 population frequency of a single allele and associated with an up to 80% risk of developing microsatellite unstable cancer (microsatellite instability - high, or MSI-H)...
2021: Frontiers in Immunology
#29
MULTICENTER STUDY
Gabriela Hobbs, Cansu Cimen Bozkus, Erin Moshier, Mikaela Dougherty, Michal Bar-Natan, Lonette Sandy, Kathryn Johnson, Julia Elise Foster, Tina Som, Molly Macrae, Hetal Marble, Mohamed Salama, Siraj M El Jamal, Nicole Zubizarreta, Martha Wadleigh, Richard Stone, Nina Bhardwaj, Camelia Iancu-Rubin, John Mascarenhas
Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by abnormal JAK-STAT signaling, chronic inflammation, cytopenias, and risk of transformation to acute leukemia. Despite improvements in the therapeutic options for patients with MF, allogeneic hematopoietic stem cell transplantation remains the only curative treatment. We previously demonstrated multiple immunosuppressive mechanisms in patients with MF, including increased expression of programmed cell death protein 1 (PD-1) on T cells compared with healthy controls...
December 14, 2021: Blood Advances
#30
COMMENT
Cansu Cimen Bozkus, Nina Bhardwaj
Despite the demonstrated efficacy and broad applicability of checkpoint blockade, the mechanisms by which it exerts its antitumor effects are incompletely understood. A recent article in Nature Medicine describes an ex vivo platform for assessing early responses to checkpoint blockade and the properties of tumor immune contexture in correlation to clinical responses.
September 13, 2021: Cancer Cell
#31
JOURNAL ARTICLE
Cansu Cimen Bozkus, Ana Belen Blazquez, Tomohiro Enokida, Nina Bhardwaj
Determining the antigen specificities of the endogenous T-cell repertoire is important for screening naturally occurring or therapy-induced T-cell immunity and may help identify novel targets for T-cell-based therapies. Here, we describe a rapid, sensitive, and high-throughput protocol for expanding antigen-specific T cells from human peripheral blood mononuclear cells in vitro following peptide stimulation and detecting antigen-specific effector cytokine formation by flow cytometry. Our approach can be applied to examining specific T-cell subsets from various tissues...
September 17, 2021: STAR protocols
#32
JOURNAL ARTICLE
Shira Weingarten-Gabbay, Susan Klaeger, Siranush Sarkizova, Leah R Pearlman, Da-Yuan Chen, Kathleen M E Gallagher, Matthew R Bauer, Hannah B Taylor, W Augustine Dunn, Christina Tarr, John Sidney, Suzanna Rachimi, Hasahn L Conway, Katelin Katsis, Yuntong Wang, Del Leistritz-Edwards, Melissa R Durkin, Christopher H Tomkins-Tinch, Yaara Finkel, Aharon Nachshon, Matteo Gentili, Keith D Rivera, Isabel P Carulli, Vipheaviny A Chea, Abishek Chandrashekar, Cansu Cimen Bozkus, Mary Carrington, Nina Bhardwaj, Dan H Barouch, Alessandro Sette, Marcela V Maus, Charles M Rice, Karl R Clauser, Derin B Keskin, Daniel C Pregibon, Nir Hacohen, Steven A Carr, Jennifer G Abelin, Mohsan Saeed, Pardis C Sabeti
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines...
July 22, 2021: Cell
#33
JOURNAL ARTICLE
Ming O Li, Natalie Wolf, David H Raulet, Leila Akkari, Mikael J Pittet, Paulo C Rodriguez, Rosandra N Kaplan, Ariel Munitz, Zemin Zhang, Sijin Cheng, Nina Bhardwaj
The tumor immune microenvironment (TIME) is a complex ecosystem that contains adaptive and innate immune cells that have tumor-promoting and anti-tumor effects. There is still much to learn about the diversity, plasticity, and functions of innate immune cells in the TIME and their roles in determining the response to immunotherapies. Experts discuss recent advances in our understanding of their biology in cancer as well as outstanding questions and potential therapeutic avenues.
June 14, 2021: Cancer Cell
#34
JOURNAL ARTICLE
Luciana R Muniz-Bongers, Christopher B McClain, Mansi Saxena, Gerold Bongers, Miriam Merad, Nina Bhardwaj
The presence of an immunosuppressive tumor microenvironment is a major obstacle in the success of cancer immunotherapies. Because extracellular matrix components can shape the microenvironment, we investigated the role of matrix metalloproteinase 2 (MMP2) in melanoma tumorigenesis. Significantly, we found that MMP2 signals pro-inflammatory pathways on antigen presenting cells which requires both toll-like receptor (TLR) 2 and TLR4. B16 melanoma cells that express MMP2 at baseline have slower kinetics in Tlr2-/-Tlr4-/- mice, implicating MMP2 in promoting tumor growth...
May 25, 2021: JCI Insight
#35
REVIEW
Tomohiro Enokida, Alvaro Moreira, Nina Bhardwaj
The immunoprevention of cancer and cancer recurrence is an important area of concern for the scientific community and society as a whole. Researchers have been working for decades to develop vaccines with the potential to alleviate these health care and economic burdens. So far, vaccines have made more progress in preventing cancer than in eliminating already established cancer. In particular, vaccines targeting oncogenic viruses, such as the human papillomavirus and the hepatitis B virus, are exceptional examples of successful prevention of virus-associated cancers, such as cervical cancer and hepatocellular carcinoma...
May 3, 2021: Journal of Clinical Investigation
#36
REVIEW
Mansi Saxena, Sjoerd H van der Burg, Cornelis J M Melief, Nina Bhardwaj
Therapeutic cancer vaccines have undergone a resurgence in the past decade. A better understanding of the breadth of tumour-associated antigens, the native immune response and development of novel technologies for antigen delivery has facilitated improved vaccine design. The goal of therapeutic cancer vaccines is to induce tumour regression, eradicate minimal residual disease, establish lasting antitumour memory and avoid non-specific or adverse reactions. However, tumour-induced immunosuppression and immunoresistance pose significant challenges to achieving this goal...
June 2021: Nature Reviews. Cancer
#37
JOURNAL ARTICLE
Nina M Lutz, Samuel R Chamberlain, Ian M Goodyer, Anupam Bhardwaj, Barbara J Sahakian, Peter B Jones, Paul O Wilkinson
BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents. METHODS: Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance...
April 23, 2021: CNS Spectrums
#38
COMMENT
Li Wang, John P Sfakianos, Kristin G Beaumont, Guray Akturk, Amir Horowitz, Robert P Sebra, Adam M Farkas, Sacha Gnjatic, Austin Hake, Sudeh Izadmehr, Peter Wiklund, William K Oh, Peter M Szabo, Megan Wind-Rotolo, Keziban Unsal-Kacmaz, Xin Yao, Eric Schadt, Padmanee Sharma, Nina Bhardwaj, Jun Zhu, Matthew D Galsky
PURPOSE: To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer. EXPERIMENTAL DESIGN: We pursued an unbiased approach using bulk RNA sequencing data from two clinical trials to discover (IMvigor 210) and validate (CheckMate 275) pretreatment molecular features associated with resistance to PD-1/PD-L1 blockade in metastatic urothelial cancer. We then generated single-cell RNA sequencing (scRNA-seq) data from muscle-invasive bladder cancer specimens to dissect the cellular composition underlying the identified gene signatures...
August 1, 2021: Clinical Cancer Research
#39
JOURNAL ARTICLE
Jenna H Newman, Nina Bhardwaj
Currently, immunotherapy is not effective for all cancer patients, partly due to an inability to mount sufficient tumor-specific T cell responses. Here, we highlight a recent study by Lhuillier et al. demonstrating that radiation potentiates neoantigen expression, eliciting CD4+ and CD8+ T cell responses and tumor growth control in mice.
April 2021: Trends in Immunology
#40
REVIEW
Alvaro Moreira, Lucie Heinzerling, Nina Bhardwaj, Philip Friedlander
Groundbreaking research in immunology and cancer biology in the last few decades has led to the discovery and development of novel therapeutics, such as immune checkpoint inhibitors and targeted therapies, which have revolutionized the clinical care of patients with metastatic melanoma. Updated data from the largest clinical trials continue to support the use of these treatment modalities, both in the metastatic and in adjuvant settings, with studies showing the predicted plateau effect on survival curves. However, with growing evidence that neoadjuvant therapy is also associated with high rates of recurrence-free survival, the question about whether patients should receive adjuvant or neoadjuvant treatment raises new questions about therapeutic options...
January 9, 2021: Cancers
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