tbuckley/cabot-search huggingface dataset:
Sickle-Cell Disease in Greece: Patient Reported Outcomes Related to Clinical Complications, Treatment Choices and Attitudes, Beliefs and Trends Affecting Potential Participation in Clinical Trials - a Greek National Multicentric Study
Authors: Sophia Delicou, Michael D. Diamantidis, Konstantinos Manganas, Eftychios Eftychiadis, Despoina Pantelidou, Alexandra Kourakli, Efthymia Vlachaki, Loukia Evliati, Ioannis Lafiatis, Evangelos Klironomos, Dimitra Kyriakopoulou, Aikaterini Xydaki, Vassiliki Bartzi, Despoina Papadopoulou, Vasileios Lazaris, Chrysoula Apostolou, Antonis Kattamis, Argiris Symeonidis
Journal: Blood (2019)
Should a Bulky Mediastinal Mass ≥7cm in the Longest Dimension be Considered an Adverse Prognostic Factor in Patients with Advanced Hodgkin Lymphoma and Negative Interim PET/CT?
Authors: Eldad J Dann, Rebeca Lopez-Alonso, Shunan Qi, Tania Mashiach, Michal Weiler-Sagie, Joachim Yahalom
Journal: Blood (2019)
Brentuximab Vedotin As Consolidation Therapy Post Hematopoietic Stem Cell Transplantation for Patients with Relapsed or Refractory Hodgkin Lymphoma: A Real World Analysis of the Colombian Experience
Authors: Bonell Patiño, Cristina Acon-Solano, Mario Pereira, Leonardo Enciso-Olivera, Diana Otero-de la Hoz, Humberto Martínez Cordero, Paola Spirko, Julio Solano-Vega, Mónica Arévalo-Zambrano, Ulrike Heider, Alejandro Ruiz-Patiño, Claudia Lucia Sossa, Angela María Peña, Claudia Marcela Chalela, Amado Karduss, Guillermo León-Basantes, Virginia Abello, Daniel Lorenzo Espinosa, Paola Guerrero, Alvaro Guerrero, Juan Manuel Herrera, Monica Osuna, Ivan Perdomo, Carmen Rosales, Paola Omaña, Natalia Villarroya, Víctor Rodriguez-Sanjuan, Jose Sandoval-Sus
Journal: Blood (2019)
A Phase 1 Study of Flotetuzumab, a CD123 x CD3 DART® Protein, Combined with MGA012, an Anti-PD-1 Antibody, in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Andrew H. Wei, Chun Yew Fong, Pau Montesinos, Maria Calbacho, Jordi Sierra Gil, Jaime Perez De Oteyza, Jacob M. Rowe, Ofir Wolach, Yishai Ofran, Yakir Moshe, Jichao Sun, Jan Baughman, Eileen McNulty, Ezio Bonvini, Jon M. Wigginton, Jan K Davidson-Moncada
Journal: Blood (2019)
Outcomes of Patients with Relapsed or Refractory Acute Myeloid Leukemia Receiving Hypomethylating Agent and Venetoclax
Authors: Hannah Asghari, Dasom Lee, Yehuda E. Deutsch, Onyee Chan, Najla Al Ali, Stephanie Boisclair, Amanda Brahim, Eric Padron, Andrew T Kuykendall, Alan F. List, Hugo F. Fernandez, Jeffrey E. Lancet, David A Sallman, Rami S. Komrokji, Kendra L. Sweet, Chetasi Talati
Journal: Blood (2019)
Safety, Efficacy, and PK of the BCL2 Inhibitor Venetoclax in Combination with Chemotherapy in Pediatric and Young Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Phase 1 Study
Authors: Seth E Karol, Todd M Cooper, Henrique Bittencourt, Lia Gore, Maureen M O'Brien, Christopher Fraser, Marion Gambart, Gunnar Cario, Christian Michel Zwaan, Jean-Pierre Bourquin, Mignon L. Loh, Hubert Caron, Betty Prine, Ahmed Hamed Salem, Kristina Unnebrink, Bo Tong, Tammy Palenski, Andrew E. Place
Journal: Blood (2019)
Characterization of Leukemic Stem Cells Heterogeneity in Chronic Myeloid Leukemia
Authors: Rebecca Warfvinge, Mikael Sommarin, Parashar Dhapola, Ulrich Pfisterer, Linda Geironson Ulfsson, Fatemeh Safi, Ram Krishna Thakur, Johan Richter, Göran Karlsson
Journal: Blood (2019)
TMIC-14. PD-L1 EXPRESSION IS NEGATIVELY CORRELATED TO OUTCOMES IN PATIENTS WITH MGMT METHYLATED PROMOTERS IN GBM
Authors: Siddhartha Srivastava, John Choi, Michael Lim
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is a high-grade glioma and is considered the most aggressive primary brain tumor with a median overall survival of 11–15 months. Methylation of the promoter of the MGMT gene, which encodes a DNA repair protein, has been shown to be a good prognostic indicator for GBM survival. It is known that GBM has elevated expression of several immune checkpoint molecules that allow the tumor to evade anti-tumor immune response. Therefore, it is important to elucidate connections between prognostic factors like methylation status and immunologic markers in the tumor microenvironment (TME) that might lead to immunosuppression. METHODS Patients with resected GBM tumor samples were identified by pathology reports as having tumors with either methylated or unmethylated MGMT promoters. Corresponding patient tumor biopsy samples were embedded in paraffin, sectioned, and then stained using specific antibodies for known immune checkpoint molecules: PD-1, PD-L1, LAG-3, TIM-3, CSF1R, and IDO-1. RESULTS In our cohort of 34 patients, 17 had methylated MGMT promoter regions and 17 did not. We found no statistically significant difference between methylated and unmethylated MGMT promoter status for immune checkpoint expression. However, we did find a statistically significant negative correlation (P&lt; 0.05) between the degree of PD-L1 expression in the TME and the progression free survival of patients with the MGMT promoter methylation phenotype. CONCLUSION Our study examined the relationship between immune checkpoint markers and methylation status of MGMT promoters in GBM. While there was no statistically significant difference between these two groups within the immunological framework of this study, there was a statistically significant negative correlation showing that increased PD-L1 expression in patients with methylated MGMT promoter tumors correlated to a worse progression free survival. Future studies are indicated to investigate the correlation between PD-L1 expression in relation to GBM treatment prognosis and its dependence on MGMT promoter methylation.
Long-Term Outcomes with Ibrutinib Versus the Prior Regimen: A Pooled Analysis in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) with up to 7.5 Years of Extended Follow-up
Authors: Simon Rule, Martin H. Dreyling, Andre Goy, Georg Hess, Rebecca Auer, Brad S. Kahl, Jose Angel Hernandez-Rivas, Keqin Qi, Sanjay Deshpande, Lori Parisi, Michael L. Wang
Journal: Blood (2019)
Autophagy in Endothelial Cells Regulates Their Hematopoiesis Supporting Ability
Authors: Yuan Kong, Xie-Na Cao, Zhong-Shi Lyu, Xiao-Dong Mo, Qi Wen, Hong-Yan Zhao, Yu-Hong Chen, Yu Wang, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang
Journal: Blood (2019)
Vascular and Parenchymal Alterations of the Liver and Liver Surveillance in Patients Who Received Inotuzumab Ozogamicin As the Standard of Care for Relapse/Refractory Acute Lymphoblastic Leukemia
Authors: Giovanni Marconi, Federico Ravaioli, Giovanni Martinelli, Elton Dajti, Maria Chiara Abbenante, Chiara Sartor, Luigina Vanessa Alemanni, Jacopo Nanni, Sarah Parisi, Giovanni Marasco, Gianluca Cristiano, Amanda Vestito, Francesca Bonifazi, Stefania Paolini, Antonio Curti, Davide Festi, Michele Cavo, Cristina Papayannidis, Antonio Colecchia
Journal: Blood (2019)
GENE-13. GENOMIC AND RADIOMIC LANDSCAPE OF IDH WILDTYPE-TERT PROMOTER MUTATION IN LOWER-GRADE GLIOMAS
Authors: Shuai Liu, Chuanbao Zhang, Xiaoguang Qiu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Recently, a rare subset of lower grade glioma (LoG), characterized by wild-type isocitrate dehydrogenase (IDH) and mutated TERT promoter (IDHWT-TERTpMut), has been highlighted for its dismal clinical behavior and classified as world health organization (WHO) grade IV. METHODS We examined this distinct tumor subset through genome-wide analysis of 745 gliomas and radiomic analysis of 129 LoGs. RESULTS We found that the prognosis and genetic lineage of IDHWT-TERTpMut LoGs were similar to those of glioblastoma. Importantly, a signature of 7 radiomic features from magnetic resonance imaging data differentiated IDHWT-TERTpMut LoGs from other LoGs. In addition, we found the radiomic related genes involved in many tumorigenic processes. CONCLUSIONS Overall, our findings suggest that the biological characteristics of IDHWT-TERTpMut LoGs and the radiomic signature could help in the non-invasive diagnosis of this tumor subtype.
<i>Notes from the Field:</i> Botulism Type E After Consumption of Salt-Cured Fish — New Jersey, 2018
Authors: Pavan V. Ganapathiraju, Radhika Gharpure, Deepam Thomas, Natalie Millet, Daniel Gurrieri, Kevin Chatham-Stephens, Janet Dykes, Carolina Luquez, Perraju Dinavahi, Sandhya Ganapathiraju, Scott Roger, Danish Abbasi, Nancy Higgins, Frances Loftus, Manish Trivedi
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
Serum concentration of VEGF, sFLT-1, and CD105 in patients with endometrial carcinoma.
Authors: Johanna Maenpaa, Sami Kristian Saarelainen, Nina Peltonen, Terho Lehtimaki, Maarit Vuento
Journal: Journal of Clinical Oncology (2012)

e15564 Background: Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The aim of this study was to compare preoperative serum levels of angiogenetic markers VEGF, sFLT-1, and CD105 (endoglin) in predicting a metastasized disease. Methods: Preoperative sera from 100 consecutive patients diagnosed for endometrial carcinoma were collected. The serum concentrations of VEGF, sFLT-1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). The results were correlated to the presence of metastases, presence of deep (≥50%) myometrial invasion and histologic grade of the tumor. Cases with other than endometrioid histology were excluded from the study. Results: Eleven patients had a metastasized disease (≥Stage IIIA, FIGO 2009 classification). The serum concentration of VEGF was higher in the group with metastases (median [range] 394 pg/mL [31-1524 pg/mL] vs. 801 pg/mL [631-1183 pg/mL], p=0.001). The concentrations of sFLT-1 and CD105 did not show statistical difference between the two groups. In the multivariable analysis, the concentration of VEGF was the sole independent factor for the presence of metastases (OR 1.003, 95% CI 1.000-1.005, p=0.019). Conclusions: Preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.
Outcomes and Toxicities of Ibrutinib in Marginal Zone Lymphoma: A Retrospective Cohort Study at a Single Institution
Authors: David M. Weiner, Nathaniel D. Robinson, Steven M. Bair, Hatcher J. Ballard, Mitchell E. Hughes, Sunita Dwivedy Nasta, Daniel J. Landsburg, Stefan K. Barta, Elise A. Chong, Stephen J. Schuster, Jakub Svoboda
Journal: Blood (2019)
Outcomes of Haploidentical Haematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Haemoglobinuria
Authors: Limin Liu, Huifen Zhou, Miao Miao, Depei Wu, Xiaowen Tang, Huiying Qiu, Yue Han, Zhengming Jin, Suning Chen, Aining Sun, Qingyuan Wang
Journal: Blood (2019)
Clinical and Genetic Features of Constitutional Partial Trisomy 8 Mosaicism (CT8M) Patients with Cytopenia
Authors: Yuta Yamada, Noriko Doki, Yuka Harada, Yuki Otsuka, Ryosuke Konuma, Hiroto Adachi, Atsushi Wada, Yuya Kishida, Tatsuya Konishi, Akihito Nagata, Yuma Noguchi, Atsushi Marumo, Junichi Mukae, Kyoko Inamoto, Takashi Toya, Aiko Igarashi, Yuho Najima, Takeshi Kobayashi, Hiroshi Yoshihashi, Hironori Harada, Hisashi Sakamaki, Kazuteru Ohashi
Journal: Blood (2019)
CBMT-08. IN VIVO EVALUATION OF PENTOSE PHOSPHATE PATHWAY ACTIVITY IN ORTHOTOPIC GLIOMA USING HYPERPOLARIZED δ-[1-13C]GLUCONOLACTONE
Authors: Georgios Batsios, Pavithra Viswanath, Peng Cao, Celine Taglang, Elavarasan Subramani, Robert Flavell, Peder Larson, Sabrina Ronen
Journal: Neuro-Oncology (2019)

Abstract The pentose phosphate pathway (PPP) generates NADPH and ribose 5-phosphate, which are involved in the scavenging of reactive oxygen species and the synthesis of nucleotides. As such, the PPP is typically upregulated in cancer cells to address the metabolic needs of rapid cell proliferation. Imaging PPP upregulation could therefore be useful in tumor assessment. One intermediate of the pathway is 6-phospho-δ-gluconolactone (6P-δ-GL), which is produced by phosphorylation of δ-gluconolactone. 6P-δ-GL is further metabolized to 6-phospho-gluconate (6PG). The goal of our study was to evaluate, for the first time, whether hyperpolarized (HP) δ-[1-13C]gluconolactone can be used to assess PPP flux and detect the presence of tumor in an orthotopic glioma rat model. Athymic nude rats bearing orthotropic U87 tumors or age-matched tumor-free controls were investigated. HP studies were performed following intravenous injection of HP δ-[1-13C]gluconolactone and metabolic images using a flyback spectral-spatial echo-planar spectroscopic imaging pulse were acquired. The data were processed using in-house Matlab code. 6P-δ-GL and 6-phospho-γ-[1-13C]gluconolactone were observed in all rats ~10 seconds after HP δ-[1-13C]gluconolactone injection, followed ~5 seconds later by production of 6PG observed at 179.3ppm. These data indicate that HP δ-[1-13C]gluconolactone likely crosses the blood-brain barrier, consistent with its transport via glucose transporters, and is rapidly metabolized. Importantly, 6PG was significantly higher in tumor voxels. The ratio of 6PG-to-6P-δ-GL was comparable in normal brain and in normal-appearing contralateral brain of tumor-bearing rats at 0.43±0.09 and 0.45±0.06 respectively (p=0.85), but significant higher in the tumor regions at 0.70±0.11 (p=0.04 and p=0.02 respectively), consistent with the elevated PPP flux that typically occurs in tumor cells. Our results indicate, to our knowledge for the first time, that metabolism of HP δ-[1-13C]gluconolactone can be assessed in the brain and that elevated 6PG production in glioma provides a potential metabolic imaging approach to probe tumor development, recurrence and response to therapy.
Trimethylated H3K27, and Di- and Trimethylated H3K4 Proteomic Profiling Distinguishes Acute Lymphoid Leukemia (ALL) from Acute Myeloid Leukemia (AML) and Associates with Overall Survival and Tyrosine Kinase Inhibitor Sensitivity in Adult ALL
Authors: Anneke D. van Dijk, Fieke W Hoff, Yihua Qiu, Mary Figueroa, Joya Chandra, Elias Jabbour, Eveline S. de Bont, Steven M. Kornblau
Journal: Blood (2019)
MRI Evaluation of Liver and Cardiac Iron Overload Impact on Hematopoietic Stem Cell Transplantation with β-Thalassemia Major
Authors: Libai Chen, Yuelin He, Jianyun Wen, Wenjing Yang, Xuan Liu, Yongsheng Ruan, Xiaoqin Feng, Chunfu Li, Xuedong Wu
Journal: Blood (2019)
Long-Term Outcomes in Patients with Chronic Myeloid Leukemia in Chronic Phase Receiving Frontline Nilotinib Versus Imatinib: Enestnd 10-Year Analysis
Authors: Timothy P. Hughes, Giuseppe Saglio, Richard A. Larson, Hagop M. Kantarjian, Dong-Wook Kim, Surapol Issaragrisil, Philipp Le Coutre, Gabriel Etienne, Carla Boquimpani, Richard E. Clark, Viviane Dubruille, Ian W. Flinn, Slawomira Kyrcz-Krzemien, Ewa Medras, Maria Zanichelli, Israel Bendit, Manu Sondhi, Ksenia Titorenko, Claire Nourry-Boulot, Paola Aimone, Andreas Hochhaus
Journal: Blood (2019)
Hand, Foot, and Mouth Disease
Authors: K. L. Lipp
Journal: BMJ (1963)

Adenovirus (Ad) vector–mediated transduction can cause hepatotoxicity during two phases, at ∼2 and 10 days after administration. Early hepatotoxicity is considered to involve inflammatory cytokines; however, the precise mechanism remains to be clarified. We examined the mechanism of early Ad vector–induced hepatotoxicity by using a conventional Ad vector, Ad-CAL2, and a modified Ad vector, Ad-E4-122aT-CAL2. Ad-E4-122aT-CAL2 harbors sequences complementary to the liver-specific miR-122a in the 3′ untranslated region of <i>E4</i>, leading to significant suppression of leaky Ad gene expression in the liver via posttranscriptional gene silencing and a significant reduction in late-phase hepatotoxicity. We found that Ad-E4-122aT-CAL2 transduction significantly attenuated acute hepatotoxicity, although Ad-E4-122aT-CAL2 and Ad-CAL2 induced comparable cytokine expression levels in the liver and spleen. IL-6, a major inflammatory cytokine induced by Ad vectors, significantly enhanced leaky Ad gene expression and cytotoxicity in primary mouse hepatocytes following Ad-CAL2 but not Ad-E4-122aT-CAL2 transduction. Furthermore, leaky Ad gene expression and cytotoxicity in Ad-CAL2–treated hepatocytes in the presence of IL-6 were significantly suppressed upon inhibition of JAK and STAT3. Ad vector–mediated acute hepatotoxicities and leaky Ad expression were significantly reduced in IL-6 knockout mice compared with those in wild-type mice. Thus, Ad vector–induced IL-6 promotes leaky Ad gene expression, leading to acute hepatotoxicity.
Association of Punitive and Reporting State Policies Related to Substance Use in Pregnancy With Rates of Neonatal Abstinence Syndrome
Authors: Laura J. Faherty, Ashley M. Kranz, Joshua Russell-Fritch, Stephen W. Patrick, Jonathan Cantor, Bradley D. Stein
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Despite the rapidly changing policy environment regarding substance use during pregnancy, information is lacking on the association of state policies with neonatal abstinence syndrome (NAS). <h3>Objective</h3> To determine if punitive or reporting state policies related to substance use during pregnancy are associated with NAS rates. <h3>Design, Setting, and Participants</h3> This repeated cross-sectional study used retrospective, difference-in-difference analysis of live births in the State Inpatient Databases from 8 US states in varying years between January 1, 2003, and December 31, 2014. States without punitive or reporting policies were compared with states with policies before and after policy enactment using logistic regression models adjusted for individual and county-level factors and state and year fixed effects. Analyses were conducted from April 10, 2019, to July 30, 2019. <h3>Exposures</h3> Time since enactment of state policies related to substance use in pregnancy, county-level rurality and unemployment, and presence of specialized treatment programs for pregnant and postpartum women in a county. <h3>Main Outcome and Measures</h3> Rates of NAS. <h3>Results</h3> Among 4 567 963 live births, 23 377 neonates (0.5%) received a diagnosis of NAS. Among neonates with NAS, 3394 (14.5%) lived in counties without any treatment programs specifically for pregnant and postpartum women, 20 323 (86.9%) lived in metropolitan counties, and 8135 (34.8%) lived in counties in the highest unemployment quartile. In adjusted analyses among neonates in states with punitive policies, odds of NAS were significantly greater during the first full calendar year after enactment (adjusted odds ratio, 1.25; 95% CI, 1.06-1.46;<i>P</i> = .007) and more than 1 full year after enactment (adjusted odds ratio, 1.33; 95% CI, 1.17-1.51;<i>P</i> &lt; .001). After regression adjustment, the annual NAS rate was 46 (95% CI, 43-48) neonates with NAS per 10 000 live births in states without punitive policies; 57 (95% CI, 48-65) neonates with NAS per 10 000 live births in states with punitive policies during the first full year after enactment; and 60 (95% CI, 56-65) neonates with NAS per 10 000 live births in states with punitive policies in effect for more than 1 full year. There was no association between reporting policies and odds of NAS. <h3>Conclusions and Relevance</h3> In this repeated cross-sectional analysis of 8 states, states with punitive policies were associated with greater odds of NAS immediately and in the longer term, but there was no association between NAS and states with reporting policies.
Baseline Mutational Status of Patients with Myelofibrosis and Anemia in the Realise Trial and Impact on Outcome
Authors: Haifa Kathrin Al-Ali, Heinz Gisslinger, Francesco Passamonti, Lynda Foltz, David M Ross, Nicola Vianelli, Alessandro M. Vannucchi, Norio Komatsu, Pierre Zachée, Ranjan Tiwari, Evren Zor, Shalini Chaturvedi, Geralyn Gilotti, Francisco Cervantes
Journal: Blood (2019)
Genomic Profiling of Mantle Cell Lymphoma Suggests Poor-Risk Profile Is Present at Diagnosis and Does Not Arise By Tumor Evolution
Authors: Erel Joffe, Anita Kumar, Serena Zheng, Manik Uppal, Kurt S. Bantilan, Preston Atteberry, David J. Straus, M. Lia Palomba, Ariela Noy, Steven M. Horwitz, Alison J. Moskowitz, Paul A. Hamlin, Matthew J Matasar, Connie Lee Batlevi, Gottfried R. von Keudell, Ahmet Dogan, Anas Younes, Andrew D. Zelenetz
Journal: Blood (2019)
Inhibiting Mitochondria Function By Bcl-2 Inhibitor Venetoclax and Complex I Inhibitor Iacs-010759 Eliminate Leukemia Cells in Pre-Clinical AML Models
Authors: Qi Zhang, Alessia Lodi, Shannon Renee Sweeney, Lina Han, Tianyu Cai, Vinitha Mary Kuruvilla, Antonio Cavazos, Helen Ma, Yoko Tabe, Joseph R Marszalek, Stefano Tiziani, Marina Y Konopleva
Journal: Blood (2019)
Domatinostat favors the immunotherapy response by modulating the tumor immune microenvironment (TIME)
Authors: Anne Catherine Bretz, Ulrike Parnitzke, Kerstin Kronthaler, Tobias Dreker, René Bartz, Frank Hermann, Astrid Ammendola, Tanja Wulff, Svetlana Hamm
Journal: Journal for ImmunoTherapy of Cancer (2019)

The efficacy of PD-(L)1 blockade depends on the composition of the tumor immune microenvironment (TIME) and is generally higher in tumors with pre-existing cytotoxic T cells (CTL) than in those with low CTL numbers. Nonetheless, a significant proportion of patients with pre-existing immunity fail to respond, indicating a therapeutic potential for combining PD-(L)1 blockade with additional immunomodulatory agents in both CTL-high and -low immune phenotypes. Here, we evaluated domatinostat (4SC-202), a class I-selective histone deacetylase (HDAC) inhibitor, for its effect on the TIME and its antitumoral efficacy using syngeneic mouse models with CTL-high or CTL-low tumors.Domatinostat was evaluated in PD-1 blockade-insensitive CTL-low (CT26) and CTL-high (C38) syngeneic models alone and in combination with different immune-inhibitory and -stimulatory approaches. Effects on the immunophenotype were assessed via flow cytometry and RNA-seq analyses. The changes in RNA-seq-based immune signatures determined in a murine setting were investigated in patient samples from the first-dose cohort of the SENSITIZE trial (NCT03278665) evaluating domatinostat combined with pembrolizumab in advanced-stage melanoma patients refractory/nonresponding to PD-1 blockade.Domatinostat increased the expression of antigen-presenting machinery (APM) genes and MHC class I and II molecules, along with CTL infiltration, in tumors of both immune phenotypes. In combination with PD-(L)1 blockade, domatinostat augmented antitumor effects substantially above the effects of single-agent therapies, displaying greater benefit in tumors with pre-existing CTLs. In this setting, the combination of domatinostat with agonistic anti-4-1BB or both PD-1 and LAG3 blockade further increased the antitumor efficacy. In CTL-low tumors, domatinostat enhanced the expression of genes known to reinforce immune responses against tumors. Specifically, domatinostat increased the expression of Ifng and genes associated with responses to pembrolizumab and nivolumab. Clinically, these findings were confirmed in patients with advanced melanoma treated with domatinostat for 14 days, who demonstrated elevated expression of APM and MHC genes, the IFNG gene, and the IFN-γ and pembrolizumab response signatures in individual tumor samples.In summary, these data suggest a promising potential of domatinostat in combination with immunotherapy to improve the outcome of refractory cancer patients.