tbuckley/cabot-search huggingface dataset:
Abstract 242: Multi-omics Profiling of Rat Offspring Exposed to Gestational Diabetes Reveals Cardiometabolic Disease Development With Age
Authors: Stephanie M Kereliuk, Prasoon Agarwal, Gabriel Brawerman, Laura Cole, Bo Xiang, Mario Fonseca, Grant Hatch, Jonathan McGavock, Vernon Dolinsky
Journal: Circulation Research (2020)

Through unknown mechanisms, fetal exposure to gestational diabetes mellitus (GDM) increases the risk for cardiovascular disease development later in life. We hypothesize that fetal exposure to GDM induces alterations in cardiomyocyte metabolism and induces left ventricular (LV) dysfunction with age. GDM was induced in female rats with a high fat (45% kcal) and sucrose diet prior to mating, throughout pregnancy and lactation. Lean control females received a low fat (10% kcal) diet. Fetal rat ventricular cardiomyocytes (FRVC) were isolated from e20.5 offspring for U-13C glucose metabolic flux analysis, mitochondrial respiration and calcium handling. The cardiac transcriptome and metabolome were measured in 3-month old offspring. LV morphology and function was assessed in the offspring from e18 to 12-months of age by transthoracic ultrasound. Offspring exposed to GDM exhibited increased LV posterior wall thickness across their life course (fetal to 12-months of age; p&lt;0.05) and impaired LV filling beginning at 6-months of age (p&lt;0.05). Consistent with the development of diastolic dysfunction in vivo, alterations in calcium flux and sarcoplasmic reticulum-dependent calcium re-uptake (1.5-fold and 1.6-fold greater, respectively) were observed in FRVC isolated from GDM offspring (p&lt;0.05). When FRVC were treated with isoproterenol, U-13C glucose metabolic flux through glycolysis and the citric acid cycle was reduced in GDM offspring, compared to Lean controls. In 3-month old offspring serum metabolomics revealed reduced citric acid cycle intermediates and an altered acylcarnitine profile. These metabolic changes corresponded to alterations in gene expression patterns identified by RNASeq associated with glucose metabolism and fatty acid transport pathways (e.g. Irs2, Slc2a4, Pfkfb2, Pdk4 and Cpt1a) . Large-scale profiling revealed GDM induced alterations in the cardiac gene expression profile leading to modified serum metabolite levels in the offspring. These alterations corresponded with mitochondrial dysfunction, impaired cardiomyocyte metabolic flux and contractility, in concert with LV hypertrophy and diastolic dysfunction in the rat offspring. Our findings identify several mechanisms that link early-life GDM exposure to the development of cardiovascular disease later in life.
Cirmtuzumab, an Anti-ROR1 Antibody, in Combination with Ibrutinib: Clinical Activity in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) from a Phase 1/2 Study
Authors: Hun Ju Lee, Michael Y. Choi, Tanya Siddiqi, William G. Wierda, Jacqueline C. Barrientos, Nicole Lamanna, Alec Goldenberg, Iris Isufi, Joseph Tuscano, Suki Subbiah, Jean L. Koff, Lori A. Leslie, Gina G Chung, Elizabeth K Weihe, Xen Ianopulos, James B. Breitmeyer, Frank J Hsu, Michael Wang, Catriona Jamieson, Thomas J. Kipps
Journal: Blood (2020)
Targeting Subtype-Specific Metabolic Preferences in Nucleotide Biosynthesis Inhibits Tumor Growth in a Breast Cancer Model
Authors: Martin P. Ogrodzinski, Shao Thing Teoh, Sophia Y. Lunt
Journal: Cancer Research (2020)

Investigating metabolic rewiring in cancer can lead to the discovery of new treatment strategies for breast cancer subtypes that currently lack targeted therapies. In this study, we used MMTV-Myc-driven tumors to model breast cancer heterogeneity, investigating the metabolic differences between two histologic subtypes, the epithelial-mesenchymal transition (EMT) and the papillary subtypes. A combination of genomic and metabolomic techniques identified differences in nucleotide metabolism between EMT and papillary subtypes. EMT tumors preferentially used the nucleotide salvage pathway, whereas papillary tumors preferred de novo nucleotide biosynthesis. CRISPR/Cas9 gene editing and mass spectrometry-based methods revealed that targeting the preferred pathway in each subtype resulted in greater metabolic impact than targeting the nonpreferred pathway. Knocking out the preferred nucleotide pathway in each subtype has a deleterious effect on in vivo tumor growth, whereas knocking out the nonpreferred pathway has a lesser effect or may even result in increased tumor growth. Collectively, these data suggest that significant differences in metabolic pathway utilization distinguish EMT and papillary subtypes of breast cancer and identify said pathways as a means to enhance subtype-specific diagnoses and treatment strategies. SIGNIFICANCE: These findings uncover differences in nucleotide salvage and de novo biosynthesis using a histologically heterogeneous breast cancer model, highlighting metabolic vulnerabilities in these pathways as promising targets for breast cancer subtypes.
Prospective Population-Based Analysis of Characteristics and Therapy Options in AML: The Case of Catalonia (PERIS Project)
Authors: Montserrat Hoyos, Ana Garrido, Montserrat Arnan, Marina Diaz-Beyá, Olga Salamero, Susana Vives, Antonio Garcia-Guiñon, David Gallardo, Marta Cervera, Ferran Vall-Llovera, Cristina Motlló, Brayan Merchan, Imma Roig Martinez, Xavier Ortin, Pável E Olivera, Anna Sureda Balari, David Valcarcel, Josep-Maria Ribera, Jordi Esteve, Jorge Sierra
Journal: Blood (2020)
VAV1-GFP Fusion Protein Generated By Intron-Based Genome Editing through CRISPR/Cas9 Leads to Spontaneous Activation in TCR Signaling
Authors: Xiaoqian Liu, Yuping Li, Xuxiang Liu, Wei Qi, Jibin Zhang, Kunal Shetty, Javeed Iqbal, Wing C. Chan
Journal: Blood (2020)
Phase 1 Study of Alvelestat, an Oral Neutrophil Elastase Inhibitor, in Patients with Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation
Authors: Annie Im, Noa G. Holtzman, Lauren M. Curtis, Laura Parsons-Wandell, Jeannette Nashed, Cody Peer, William D. Figg, Amisha Barochia, Jeremy J. Rose, Frances T. Hakim, Steven Z. Pavletic
Journal: Blood (2020)
Phase III Study of Daratumumab/rhuph20 (nsc- 810307) + Lenalidomide or Lenalidomide As Post-Autologous Stem Cell Transplant Maintenance Therapyin Patients with Multiple Myeloma (mm) Using Minimal Residual Disease Todirect Therapy Duration (DRAMMATIC study): SWOG s1803
Authors: Amrita Krishnan, Antje Hoering, Parameswaran Hari, Rachael Sexton, Robert Z. Orlowski
Journal: Blood (2020)
Feasibility of Peri-Transfusion Quality of Life Assessment for Patients with Myelodysplastic Syndromes
Authors: Gregory A. Abel, Heidi D. Klepin, Emily S. Magnavita, Tim Jaung, Rory M. Shallis, Nupur E. Bahl, Rebecca Dellinger-Johnston, Eric S. Winer, Amer M. Zeidan
Journal: Blood (2020)
Rare Inherited Defects of the Complement System in Purpura Fulminans
Authors: Pavan Bendapudi, Justine Ryu, Onuralp Soylemez, Betty Rouaisnel, Meaghan Colling, Bryce Pasko, Alissa Robbins, Michael Bouzinier, Lindsay Tomczak, Sanjay Ram, Agnes Toth-Petroczy, Joel Krier, Elizabeth Fieg, Walter Dzik, James Hudspeth, Olga Pozdnyakova, Valentina Nardi, Richard Maas, Julie-Aurore Losman
Journal: Blood (2020)
The Clinical Severity of Alpha-2 Globin Gene Variants: Homozygosity for Hb Agrinio (<i>HBA2</i>: c.89T&amp;gt;C) Leads to Severe Antenatal Anemia, about 8 Cases in 3 Families
Authors: Claire Berger, Philippe Joly, Serge Pissard, Sandrine Baron-Joly, Yoann Huguenin, Aurélie Cantais, Sophie Brun, Cecile GED, Catherine Badens, Muriel Giansily-Blaizot, Aguilar-Martinez Patricia, Isabelle Thuret
Journal: Blood (2020)
Erratum. The Relationship Between CGM-Derived Metrics, A1C, and Risk of Hypoglycemia in Older Adults With Type 1 Diabetes. Diabetes Care 2020;43:2349–2354
Authors: Elena Toschi, Christine Slyne, Kayla Sifre, Rachel O’Donnell, Jordan Greenberg, Astrid Atakov-Castillo, Sam Carl, Medha Munshi
Journal: Diabetes Care (2020)

glucose management indicator (GMI) was incorrect as written in the above-referenced article.The sentence "GMI percentage was calculated as (3.31 1 0.02392) 3 mean glucose in mg/dL" is changed to read as follows:"GMI percentage was calculated as 3.31 1 (0.02392 3 mean glucose in mg/dL).
LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer
Authors: Yue‐Tao Tan, Jin‐Fei Lin, Ting Li, Jia‐Jun Li, Rui‐Hua Xu, Huai‐Qiang Ju
Journal: Cancer Communications (2020)

Abstract Altered metabolism is a hallmark of cancer, and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors. It is well recognized that long noncoding RNAs (lncRNAs) regulate energy metabolism in cancer. However, lncRNA‐mediated posttranslational modifications and metabolic reprogramming are unclear at present. In this review, we summarized the current understanding of the interactions between the alterations in cancer‐associated energy metabolism and the lncRNA‐mediated posttranslational modifications of metabolic enzymes, transcription factors, and other proteins involved in metabolic pathways. In addition, we discuss the mechanisms through which these interactions contribute to tumor initiation and progression, and the key roles and clinical significance of functional lncRNAs. We believe that an in‐depth understanding of lncRNA‐mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.
Final Analysis of the International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL in Response after R-CHOP, the Remarc Study from Lysa
Authors: Catherine Thieblemont, Maria Gomes da Silva, Olivier Casasnovas, Hervé Ghesquieres, Gandhi Laurent Damaj, Judith Trotman, Pierre Feugier, Corinne Haioun, Richard Greil, Dolores Caballero, Armando Lopez-Guillermo, Sebastian Grosicki, Koen Van Eygen, Sylvia Snauwaert, Ewa Lech-Marańda, Sonja Heibl, John Catalano, Amos Cohen, Anne Cairoli, Philippe Gaulard, Franck Morschhauser, Herve Tilly
Journal: Blood (2020)
Identification of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies
Authors: Wu Yin, Nie Zhe, Andrew Placzek, Michael Trzoss, Goran Krilov, Shulu Feng, Morgan Lawrenz, Robert Pelletier, George Lai, Jeff Bell, David Calkins, Mary Grimes, Wayne Tang, Fiona McRobb, Aleksey Gerasyuto, Victoria Feher, Sayan Mondal, Kristian Jensen, Hamish Wright, Karen Akinsanya
Journal: Blood (2020)
Targeted inhibition of PI3 kinase/mTOR specifically in fibrotic lung fibroblasts suppresses pulmonary fibrosis in experimental models
Authors: Suraj U. Hettiarachchi, Yen-Hsing Li, Jyoti Roy, Fenghua Zhang, Estela Puchulu-Campanella, Spencer D. Lindeman, Madduri Srinivasarao, Konstantin Tsoyi, Xiaoliang Liang, Ehab A. Ayaub, Cheryl Nickerson-Nutter, Ivan O. Rosas, Philip S. Low
Journal: Science Translational Medicine (2020)

Inhibition of phosphatidylinositol 3-kinase in lung myofibroblasts reduced symptoms of IPF in rodents and in vitro human samples.
Three Distinct Groups of Phenotype Severity in Beta-Thalassemia
Authors: Aurelio Maggio, Angela Vitrano, Antonella Meloni, Walter Addario Pollina, Mehran Karimi, Amal El-Beshlawy, Mahmoud Hajipour, Vito Di Marco, Saqib Hussain Ansari, Aldo Filosa, Paolo Ricchi, Adriana Ceci, Shahina Daar, Sylvia Titi Singer, J F Borgio, Alessia Pepe, Salvatore Scondotto, Gabriella Dardanoni, Massimiliano Sacco, Laura Pistoia, Rita Barone, Fedele Bonifazi, Lorella Pitrolo, Elliott P. Vichinsky
Journal: Blood (2020)
Characterization of Cytokine Release Syndrome in the KarMMa Study of Idecabtagene Vicleucel (ide-cel, bb2121) for Relapsed and Refractory Multiple Myeloma
Authors: Ankit Kansagra, Yi Lin, Jesus G. Berdeja, Nina Shah, Albert Oriol, Ibrahim Yakoub-Agha, Hermann Einsele, Alessandro Rambaldi, Anna Truppel-Hartmann, Everton Rowe, Julie Wang, Amit Agarwal, Timothy B. Campbell, Sagar Lonial
Journal: Blood (2020)
Treatment Efficacy and Outcomes in HIV-Related Plasmablastic Lymphoma: The Results of Multicenter Retrospective Study in Russia
Authors: Marina O. Popova, Yuliya A. Rogacheva, Ivan V. Tsigankov, Marina Demchenkova, Tatiana V. Shneider, Kirill V. Lepik, Vadim Baykov, Natalia B. Mikhailova, Aleksandr D. Kulagin
Journal: Blood (2020)
Recurrent <i>Crebbp</i> Mutations in Follicular Lymphoma Appear Localized to the Committed B-Cell Lineage
Authors: Joseph G Schroers-Martin, Joanne Soo, Gabriel Brisou, Florian Scherer, David M. Kurtz, Brian Sworder, Michael S. Khodadoust, Michael C. Jin, Agnès Bru, Chih Long Liu, Henning Stehr, Paolo Vineis, Yasodha Natkunam, Bertrand Nadel, Maximilian Diehn, Sandrine Roulland, Ash A. Alizadeh
Journal: Blood (2020)
CD22-Directed CAR T-Cell Therapy Mediates Durable Complete Responses in Adults with Relapsed or Refractory Large B-Cell Lymphoma after Failure of CD19-Directed CAR T-Cell Therapy and High Response Rates in Adults with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Authors: John H. Baird, Matthew J. Frank, Juliana Craig, Shabnum Patel, Jay Y. Spiegel, Bita Sahaf, Sheren F. Younes, Jean S. Oak, Yasodha Natkunam, Zachary Ehlinger, Warren D. Reynolds, Sally Arai, Laura J. Johnston, Robert Lowsky, Robert S. Negrin, Andrew R. Rezvani, Parveen Shiraz, Surbhi Sidana, Wen-Kai Weng, Liora M. Schultz, Sneha Ramakrishna, Kara L Davis, Steven A. Feldman, Crystal L. Mackall, David B. Miklos, Lori S. Muffly
Journal: Blood (2020)
Phase II Study of Daratumumab in Combination with Azacitidine and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients Previously Treated with Daratumumab: Darazadex
Authors: Swetha Kambhampati, Sandy W. Wong, Thomas Martin, Jeffrey L. Wolf, Priya Choudhry, William Karlon, Arun P. Wiita, Nina Shah
Journal: Blood (2020)
Genetic deletion of p66shc and/or cyclophilin D results in decreased pulmonary vascular tone
Authors: Mareike Gierhardt, Oleg Pak, Akylbek Sydykov, Simone Kraut, Julia Schäffer, Claudia Garcia, Christine Veith, Esraa M Zeidan, Monika Brosien, Karin Quanz, Azadeh Esfandiary, Alireza Saraji, Stefan Hadzic, Baktybek Kojonazarov, Jochen Wilhelm, Hossein A Ghofrani, Ralph T Schermuly, Werner Seeger, Friedrich Grimminger, Christiane Herden, Rainer Schulz, Norbert Weissmann, Jacqueline Heger, Natascha Sommer
Journal: Cardiovascular Research (2020)

The pulmonary vascular tone and hypoxia-induced alterations of the pulmonary vasculature may be regulated by the mitochondrial membrane permeability transition pore (mPTP) that controls mitochondrial calcium load and apoptosis. We thus investigated, if the mitochondrial proteins p66shc and cyclophilin D (CypD) that regulate mPTP opening affect the pulmonary vascular tone.
Contrast‐Enhanced Ultrasonography–Based Hepatic Perfusion for Early Prediction of Prognosis in Acute Liver Failure
Authors: Hidekatsu Kuroda, Tamami Abe, Yudai Fujiwara, Tomoaki Nagasawa, Yuji Suzuki, Keisuke Kakisaka, Yasuhiro Takikawa
Journal: Hepatology (2020)

Background and Aims Acute liver failure (ALF) is a rare but dramatic clinical syndrome characterized by massive hepatic necrosis leading to multiorgan failure. It is difficult to predict the outcomes in patients with ALF using existing prognostic models. We aimed to analyze hepatic perfusion using contrast‐enhanced ultrasound and Doppler ultrasound in patients with ALF and investigate its utility as a prognostic biomarker. Approach and Results In this prospective observational study, 208 patients with acute liver injury/ALF were enrolled from 2015 to 2019. We evaluated 50 consecutive patients with ALF with Doppler ultrasound and contrast‐enhanced ultrasound performed on admission. The cases were divided into the following two groups: survivors (recovered without surgical intervention) and nonsurvivors (died of ALF or underwent liver transplantation). The time to peak and peak intensity of hepatic artery, portal vein, hepatic vein, and liver parenchyma were calculated using the time‐intensity curve analysis. The hepatic artery (HA) resistive index was calculated using the fast Fourier transform analysis of Doppler ultrasound. The time interval (TI) between the time to peak of HA and liver parenchyma (LP) was significantly shorter in the nonsurvivors than in the survivors ( P &lt; 0.0001). The area under the receiver operating curve values for TI (HA, LP), Japanese scoring system, HE prediction model, Model for End‐Stage Liver Disease score, and King’s College Hospital criteria for the prediction of poor prognosis were 0.953, 0.914, 0.861, 0.816, and 0.731, respectively. The most appropriate cutoff value of TI (HA, LP) was 6.897 seconds; the sensitivity, specificity, positive and negative predictive values were 94.4%, 90.6%, 85.0%, and 96.7%, respectively. Conclusions TI (HA, LP) accurately predicts the outcome in patients with ALF and may be useful in clinical decision making.
Response to ‘Neither earlier not late tocilizumab improved outcomes in the intensive care unit patients with COVID-19 in a retrospective cohort study’ by Moiseev<i>et al</i>
Authors: Sofia Ramiro, Robert B M Landewé, Rémy Mostard
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the letter from Moiseev et al 1 on our COVID High-intensity Immunosuppression in Cytokine storm syndrome study.2 In our study, we have used an immunosuppressive strategy composed by glucocorticoids in the first line, followed, in case of insufficient response, by tocilizumab in patients with COVID-19-associated cytokine storm syndrome (CSS). Moiseev et al share with us the results of their study in which they have treated patients with COVID-19 with tocilizumab. In a retrospective study, the authors compared the outcomes of patients treated with tocilizumab with those of patients not treated with it. Patients could receive tocilizumab in the presence of bilateral pneumonia involving at least 50% of lung tissue and requiring …
Combination of Osimertinib and Bevacizumab as First-line Treatment for Patients With Metastatic <i>EGFR</i>-Mutant Lung Cancers—Reply
Authors: Adam J. Schoenfeld, Helena A. Yu
Journal: JAMA Oncology (2020)

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Quantitative analysis and virulence phenotypes of atypical enteropathogenic <i>Escherichia coli</i> (EPEC) acquired from diarrheal stool samples from a Midwest US hospital
Authors: MJ Carlino, SE Kralicek, SA Santiago, LM Sitaraman, AT Harrington, Gail A. Hecht
Journal: Gut Microbes (2020)

Infectious diarrhea causes approximately 179 million illnesses annually in the US. Multiplex PCR assays for enteric pathogens detect enteropathogenic Escherichia coli (EPEC) in 12-29% of diarrheal stool samples from all age groups in developed nations. The aim of this study was to isolate and characterize EPEC from diarrhea samples identified as EPEC positive by BioFire Gastrointestinal Panel (GIP). EPEC is the second most common GIP-detected pathogen, equally present in sole and mixed infections peaking during summer months. EPEC bacterial load is higher in samples with additional pathogens. EPEC-GIP-positive stool samples were cultured on MacConkey II agar and analyzed by colony PCR for eaeA and bfpA to identify and classify EPEC isolates as typical (tEPEC) or atypical (aEPEC). EPEC were not recovered from the majority of stool samples with only 61 isolates obtained from 277 samples; most were aEPEC from adults. bfpA-mRNA was severely diminished in 3 of 4 bfpA-positive isolates. HeLa and SKCO-15 epithelial cells were infected with EPEC isolates and virulence-associated phenotypes, including adherence pattern, attachment level, pedestal formation, and tight junction disruption, were assessed. All aEPEC adherence patterns were represented with diffuse adherence predominating. Attachment rates of isolates adhering with defined adherence patterns were higher than tEPEC lacking bfpA (ΔbfpA). The majority of isolates formpedestals. All but one isolate initially increases but ultimately decreases transepithelial electrical resistance of SKCO-15 monolayers, similar to ΔbfpA. Most isolates severely disrupt occludin; ZO-1 disruption is variable. Most aEPEC isolates induce more robust virulence-phenotypes in vitro than ΔbfpA, but less than tEPEC-E2348/69.
Outcomes of Patients (Pts) in ZUMA-9, a Multicenter, Open-Label Study of Axicabtagene Ciloleucel (Axi-Cel) in Relapsed/Refractory Large B Cell Lymphoma (R/R LBCL) for Expanded Access and Commercial Out-of-Specification (OOS) Product
Authors: Caron A. Jacobson, Frederick L. Locke, David B. Miklos, Julie M. Vose, Yi Lin, Lihua E Budde, David G. Maloney, Samantha Jaglowski, Peter A. Riedell, Lazaros J. Lekakis, Miguel-Angel Perales, Jenny J. Kim, Jun Kawashima, Yin Yang, John M. Rossi, Lovely Goyal, Sattva S. Neelapu
Journal: Blood (2020)
iPSC-derived NK cells maintain high cytotoxicity and enhance in vivo tumor control in concert with T cells and anti–PD-1 therapy
Authors: Frank Cichocki, Ryan Bjordahl, Svetlana Gaidarova, Sajid Mahmood, Ramzey Abujarour, Hongbo Wang, Katie Tuininga, Martin Felices, Zachary B. Davis, Laura Bendzick, Raedun Clarke, Laurel Stokely, Paul Rogers, Moyar Ge, Megan Robinson, Betsy Rezner, David L. Robbins, Tom T. Lee, Dan S. Kaufman, Bruce R. Blazar, Bahram Valamehr, Jeffrey S. Miller
Journal: Science Translational Medicine (2020)

The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors, such as programmed cell death 1 (PD-1), or their ligands, such as PD-L1, has transformed the oncology landscape. However, durable tumor regression is limited to a minority of patients. Therefore, combining immunotherapies with those targeting checkpoint inhibitory receptors is a promising strategy to bolster antitumor responses and improve response rates. Natural killer (NK) cells have the potential to augment checkpoint inhibition therapies, such as PD-L1/PD-1 blockade, because NK cells mediate both direct tumor lysis and T cell activation and recruitment. However, sourcing donor-derived NK cells for adoptive cell therapy has been limited by both cell number and quality. Thus, we developed a robust and efficient manufacturing system for the differentiation and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs). iPSC-derived NK (iNK) cells produced inflammatory cytokines and exerted strong cytotoxicity against an array of hematologic and solid tumors. Furthermore, we showed that iNK cells recruit T cells and cooperate with T cells and anti-PD-1 antibody, further enhancing inflammatory cytokine production and tumor lysis. Because the iNK cell derivation process uses a renewable starting material and enables the manufacturing of large numbers of doses from a single manufacture, iNK cells represent an "off-the-shelf" source of cells for immunotherapy with the capacity to target tumors and engage the adaptive arm of the immune system to make a "cold" tumor "hot" by promoting the influx of activated T cells to augment checkpoint inhibitor therapies.