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Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control

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Heliyon 2025年第1期11卷 e41633页

作者： Adedeji, Eunice O. Ogunlana, Olubanke O. Oduselu, Gbolahan O. Koenig, Rainer Adebiyi, Ezekiel Soremekun, Opeyemi S. Fatumo, Segun Covenant University Bioinformatics Research (CUBRe) Covenant University Ogun State Ota Nigeria Department of Biochemistry Covenant University Ogun State Ota Nigeria Department of Biology University of York York United Kingdom Covenant Applied Informatics and Communication Africa Centre of Excellence Covenant University Ota Nigeria Institute for Infectious Diseases and Infection Control (IIMK RG Systems Biology) Jena University Hospital Am Klinikum 1 Jena 07747 Germany African Center of Excellence in Bioinformatics & Data Intensive Science Makerere University Kampala 10218 Uganda Division of Applied Bioinformatics German Cancer Research Center (DKFZ) G200 Im Neuenheimer Feld 280 Heidelberg 69120 Germany The African Computational Genomics (TACG) Research Group MRC/UVRI and LSHTM Entebbe Uganda Precision Healthcare University Research Institute Queen Mary University of London United Kingdom Department of Non-Communicable Disease Epidemiology London School of Hygiene & Tropical Medicine United Kingdom

Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of Anopheles gambiae 3HKT (Ag3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against Anopheles gambiae 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4. The top three identified hits were subjected to 300 ns molecular dynamics simulation using AMBER 18 and ADMET analysis using SWISSADME predictor and ADMETSAR. Replacement of alkyl attachment on C5 of isoxazole or oxadiazole derivative with a cycloalkyl group yielded compounds with lower binding energy than their straight chain counterparts. The top three compounds were brominated compounds, 2‐[3‐(4‐bromophenyl)‐1,2‐oxazol‐5‐yl]cyclopentane‐1‐carboxylic acid, 2-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, 3-[3-(4-bromo-2-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, and they had binding energies of −8.58, −8.25, and −8.18 kcal/mol in virtual screening against 2CH2 protein target, respectively. These compounds were predicted to be less toxic than temephos, a standard larvicide and more biodegradable than previously reported inhibitors. The three compounds exhibited a greater stabilizing effect on 2CH2 protein target than 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid, a previously reported inhibitor candidate with good larvicidal activity on Aedes aegypti. Further thermodynamic calculations revealed that the top three compounds possessed total binding energies (ΔG_bind) of −26.64 kcal/mol, −24.26 kcal/mol and −14.11 kcal/mol, respectively, as compared to −12.02 kcal/mol for 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid. These compounds could be better larvicides than previously reported isoxazole or oxadiazole derivatives and safer than temephos. © 2025 The Authors

关键词： 1,2,4-Oxadiazole 3HKT Isoxazoles Larvicide Mosquito Vector control

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The role of MLH1, MSH2 and MSH6 in the development of colorectal cancer in Uganda

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BMC Cancer 2025年第1期25卷 1-13页

作者： Wismayer, Richard Matthews, Rosie Whalley, Celina Kiwanuka, Julius Kakembo, Fredrick Elishama Thorn, Steve Wabinga, Henry Odida, Michael Tomlinson, Ian Department of Surgery Masaka Regional Referral Hospital Masaka Uganda Department of Surgery Faculty of Health Sciences Equator University of Science and Technology Masaka Uganda Department of Surgery Faculty of Health Sciences Habib Medical School IUIU University Kampala Uganda Department of Pathology School of Biomedical Sciences College of Health Sciences Makerere University Kampala Uganda Institute of Genetics and Cancer College of Medicine and Veterinary Medicine University of Edinburgh Edinburgh United Kingdom Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham United Kingdom Department of Epidemiology and Biostatistics College of Health Sciences Makerere University Kampala Uganda Department of Immunology and Molecular Biology School of Biomedical Sciences College of Health Sciences Makerere University Kampala Uganda Department of Pathology Faculty of Medicine Gulu University Gulu Uganda Department of Oncology University of Oxford Oxford United Kingdom African Centre of Excellence in Bioinformatics and Data Intensive Sciences Infectious Diseases Institute Makerere University Kampala Uganda

Introduction: In Uganda, colorectal cancer (CRC) is steadily increasing according to the Kampala Cancer Registry. In the West, microsatellite instability is detected in 90% of hereditary nonpolyposis colon cancers (HNPCC) which account for 1–2% of all CRC, and 15% of sporadic CRC. Germline mutations in MLH1 and MSH2 account for 90% of HNPCC in the West, whilst the remainder of cases are due to mutations in MSH6 and PMS2. The aim of this study was to determine the microsatellite instability (MSI) status and determine the proportions of MLH1, MSH2, and MSH6 pathological mutations in Ugandan CRC patients. Methodology: This was a cross-sectional study carried out between 1st January 2008 to 15th September 2021. Patients were recruited prospectively from 16th September 2019 to 16th September 2021, from Masaka Regional Referral Hospital, Mulago National Referral Hospital, Uganda Martyrs’ Hospital Lubaga and Mengo Hospital. From 1st January 2008 to 15th September 2019, CRC FFPE tissue blocks were obtained from the archives of the Department of Pathology, Makerere University. data was abstracted from the medical case files for demographics, topography and stage. The histopathological subtype and grade of CRC were obtained by two consultant pathologists from the H&E slides. DNA was extracted from CRC formalin-fixed paraffin-embedded (FFPE) tissue blocks. Library preparation was completed using the Qiagen custom design panel. The custom panel represented 56 genes. The MLH-1, MSH2, MSH6, BRAF and KRAS genes were sequenced using the above library preparation and NGS sequencing. The MSI status was obtained if one of the MSI genes, MLH1, MSH2 or MSH6 was pathologically mutated. If none of the genes was pathologically mutated it was considered MSI negative, microsatellite stable (MSS). Immunohistochemistry was carried out to determine whether MLH1 and PMS2 was MMR proficient or deficient. Categorical data was summarized using frequencies and proportions corresponding to each of th

关键词： Colorectal cancer Immunohistochemistry Microsatellite instability (MSI) Microsatellite stable (MSS) Uganda

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Impact of multiple maize technology package adoption on the production efficiency and food security of smallholder farmers in Ethiopia: Evidence from the Sidama region

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Heliyon 2025年第1期11卷 e41280页

作者： Guye, Ashenafi Tefera, Tewodros Sileshi, Million Edriss, Abdi-Khalil Haramaya University College of Agriculture and Environmental Science School of Agricultural Economics and Agri-business Dire Dawa Ethiopia Hawassa University Daye Campus Department of Agribusiness and Value Chain Management Daye Ethiopia REFOOTURE Ethiopia Project Manager and Co-strategic Lead Addis Ababa Ethiopia Lilongwe University of Agriculture and Natural Resources Department of Agricultural Economics and African Center of Excellence Agricultural Policy Analysis–Big Data Lilongwe Malawi

This study aimed to investigate the individual or combined impacts of multiple maize technology package adoption on the production efficiency and food security of smallholder farmers in the selected districts of Sidama region of Ethiopia. The cross-sectional data of 424 sample farmers owing 545 maize plots were collected using multistage sampling approaches. The selection-bias corrected multinomial endogenous switching regression (MESR) model was employed to assess the impact of improved maize seed, chemical fertilizers, and row planting adoption on the production efficiency and food security of smallholder maize-producing farmers. In the first stage of the MESR model, the multinomial logit was used to examine the determinants of adoption. The results of the model showed that a male household head, greater household size, land size, tropical livestock unit, oxen, several plots, extension contact, credit access, and membership in farmers-based organizations were significant factors affecting the adoption of improved maize seed, chemical fertilizer, and row planting. In addition, the results from the second stage impact estimation demonstrated that the adoption of maize technology packages, both individually and in combination, significantly impacts the production efficiency and food security of farming households. Moreover, the simultaneous adoption of two or more technology packages has a greater impact than it does in isolation. The highest technical, allocative, and economic efficiency and food consumption scores, which are 33 %, 37 %, 47 %, and 17, respectively, were achieved when farm households adopted all technology packages simultaneously, followed by the adopters of two packages in combination. Therefore, the policies and strategies aimed at increasing farmers’ production efficiency and food security should address the important variables identified and promote wider adoption in combination to realize the utmost benefit. © 2024 The Author(s)

关键词： Adoption impact Chemical fertilizer Food security Improved seed MESR model Production efficiency Row planting

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Translation dysregulation in cancer as a source for targetable antigens

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Cancer Cell 2025年第5期43卷 823-840.e18,20页

作者： Weller, Chen Bartok, Osnat McGinnis, Christopher S. Palashati, Heyilimu Chang, Tian-Gen Malko, Dmitry Shmueli, Merav D. Nagao, Asuteka Hayoun, Deborah Murayama, Ayaka Sakaguchi, Yuriko Poulis, Panagiotis Khatib, Aseel Erlanger Avigdor, Bracha Gordon, Sagi Cohen Shvefel, Sapir Zemanek, Marie J. Nielsen, Morten M. Boura-Halfon, Sigalit Sagie, Shira Gumpert, Nofar Yang, Weiwen Alexeev, Dmitry Kyriakidou, Pelgia Yao, Winnie Zerbib, Mirie Greenberg, Polina Benedek, Gil Litchfield, Kevin Petrovich-Kopitman, Ekaterina Nagler, Adi Oren, Roni Ben-Dor, Shifra Levin, Yishai Pilpel, Yitzhak Rodnina, Marina Cox, Jürgen Merbl, Yifat Satpathy, Ansuman T. Carmi, Yaron Erhard, Florian Suzuki, Tsutomu Buskirk, Allen R. Olweus, Johanna Ruppin, Eytan Schlosser, Andreas Samuels, Yardena Department of Molecular Cell Biology Weizmann Institute of Science Rehovot 7610001 Israel Department of Pathology Stanford University Stanford 94305 CA United States Parker Institute for Cancer Immunotherapy San Francisco 94129 CA United States Department of Cancer Immunology Institute for Cancer Research Oslo University Hospital Oslo 0379 Norway Precision Immunotherapy Alliance University of Oslo Oslo Norway Cancer Data Science Laboratory Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda 20892 MD United States Department of Systems Immunology Weizmann Institute of Science Rehovot 7610001 Israel Department of Chemistry and Biotechnology of Engineering The University of Tokyo Tokyo 113-8656 Japan Department of Physical Biochemistry Max Planck Institute for Multidisciplinary Sciences Göttingen 37077 Germany Department of Pathology Sackler School of Medicine Tel Aviv University Tel Aviv 69978 Israel Department of Immunology and Regenerative Biology Weizmann Institute of Science Rehovot 7610001 Israel Computational Systems Biochemistry Research Group Max-Planck Institute of Biochemistry Martinsried 82152 Germany Department of Veterinary Resources Weizmann Institute of Science Rehovot 7610001 Israel Tissue Typing and Immunogenetics Unit Hadassah Hebrew University Hospital Jerusalem 9112102 Israel CRUK Lung Cancer Centre of Excellence University College London Cancer Institute London WC1E 6DD United Kingdom Tumour Immunogenomics and Immunosurveillance Laboratory University College London Cancer Institute London WC1E 6DD United Kingdom Department of Life Science Core Facilities Weizmann Institute of Science Rehovot 7610001 Israel Bioinformatics Unit Department of Life Sciences Core Facilities Weizmann Institute of Science Rehovot 7610001 Israel de Botton Institute for Protein Profiling the Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Rehovot

Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized as foreign by T cells. Protein synthesis in malignant cells is dysregulated, which may result in the generation and presentation of aberrant peptides that can be exploited for T cell-based therapies. To investigate the role of translational dysregulation in immunological tumor control, we disrupt translation fidelity by deleting tRNA wybutosine (yW)-synthesizing protein 2 (TYW2) in tumor cells and characterize the downstream impact on translation fidelity and immunogenicity using immunopeptidomics, genomics, and functional assays. These analyses reveal that TYW2 knockout (KO) cells generate immunogenic out-of-frame peptides. Furthermore, Tyw2 loss increases tumor immunogenicity and leads to anti-programmed cell death 1 (PD-1) checkpoint blockade sensitivity in vivo. Importantly, reduced TYW2 expression is associated with increased response to checkpoint blockade in patients. Together, we demonstrate that defects in translation fidelity drive tumor immunogenicity and may be leveraged for cancer immunotherapy. © 2025 The Author(s)

关键词： cancer immunopeptidome immune checkpoint blockade neoantigens non-canonical peptides translation fidelity

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Employing Hexahydroquinolines as PfCDPK4 Inhibitors to Combat Malaria Transmission: An Advanced Computational Approach

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Advances and Applications in bioinformatics and Chemistry 2024年 17卷 83-105页

作者： Oduselu, Gbolahan O Elebiju, Oluwadunni F. Ogunnupebi, Temitope A. Akash, Shopnil Ajani, Olayinka O. Adebiyi, Ezekiel Covenant University Bioinformatics Research (CUBRe) Covenant University OG Ota Nigeria Department of Chemistry Covenant University OG Ota Nigeria Department of Pharmacy Daffodil International University Dhaka Bangladesh African Center of Excellence in Bioinformatics & Data Intensive Science Makerere University Kampala Uganda Division of Applied Bioinformatics German Cancer Research Center (DKFZ) Heidelberg Germany

Background: Existing antimalarial drugs primarily target blood-stage parasites, but there is a need for transmission-blocking drugs to combat malaria effectively. Plasmodium falciparum Calcium-dependent Protein Kinase 4 (CDPK4) is a promising target for such drugs. This study employed advanced in silico analyses of hexahydroquinolines (HHQ) derivatives to identify PfCDPK4 inhibitors capable of disrupting malaria transmission. Structure-based virtual screening (SBVS) was employed to discover HHQ derivatives with the highest binding affinities against the 3D structure of PfCDPK4 (PDB 1D: 4QOX). Methods: Interaction analysis of protein-ligand complexes utilized Discovery Studio Client, while druglikeness and ADMET properties were assessed using SwissADME and pkCSM web servers, respectively. Quantum mechanical calculations of the top hits were conducted using density functional theory (DFT), and GROMACS was employed to perform the molecular dynamics (MD) simulations. Binding free energy was predicted using the *** tool from the AMBER package. Results: SBVS identified ten best hits possessing docking scores within the range of −11.2 kcal/mol and −10.6 kcal/mol, surpassing the known inhibitor, BKI-1294 (−9.9 kcal/mol). Among these, 4-[4-(Furan-2-carbonyl)piperazin-1-yl]-1-(naphthalen-2-ylmethyl)- 2-oxo-4a,5,6,7,8,8a-hexahydroquinoline-3-carbonitrile (PubChem ID: 145784778) exhibited the highest binding affinity (−11.2 kcal/ mol) against PfCDPK4. Conclusion: Comparative analysis of this compound with BKI-1294 using advanced computational approaches demonstrated competitive potential. These findings suggest the potential of 4-[4-(Furan-2-carbonyl)piperazin-1-yl]-1-(naphthalen-2-ylmethyl)- 2-oxo-4a,5,6,7,8,8a-hexahydroquinoline-3-carbonitrile as a promising PfCDPK4 inhibitor for disrupting malaria transmission. However, further experimental studies are warranted to validate its efficacy and safety profile. © 2024 Oduselu et al.

关键词： antimalarial drugs drug design gametocidal activity malaria molecular dynamics

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Mycotoxin’s Infections and Prevention Methods: State of the Art

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Agricultural sciences 2021年第11期12卷 1269-1285页

作者： Ishimwe Viviane Emmanuel Masabo Habiyaremye Joseph Mitsindo Rene Elias Bizuru African Center of Excellence in Internet of Things University of Rwanda Kigali Rwanda African Center of Excellence in Data Science University of Rwanda Kigali Rwanda

Fungi that attack field crops and contaminate agricultural commodities produce mycotoxins when conditions are favorable. These are specialized metabolites made of poisonous chemical compounds created by bacteria, fungi, or plants that aren’t involved in the organism’s usual growth, development, or reproduction. They have an adversarial hold on humans, wildlife, and the agricultural sector, resulting in mysterious ailments and economic disruptions. Mycotoxins-tainted food and fodder can be found all over the world, posing a global concern. Consumption of contaminated food and fodder is a typical cause of epidemic outbreaks. Other mycotoxins have been associated with esophageal cancer and neural tube defects (NTDs);the immunotoxin deoxynivalenol (DON) causes diarrhea when combined with trichothecenes, and ochratoxin A (OTA) has been linked to kidney failure. The direct market costs associated with missed trade or lower revenues owing to tainted food or feed could be viewed as the economic repercussions of mycotoxins on human society. This review describes frequent groups of mycotoxins in detail, their impact on global health, their impact on the socio-economy;the methods of detection and prevention of these mycotoxins.

关键词： Mycotoxins Global Health Impact Socio-Economy Impact Mycotoxin’s Detection Prevention Methods

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369 Precision education and generative AI in surgery utilization study: A framework for global surgical education

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Journal of Clinical and Translational science 2025年第s1期9卷 114-114页

作者： Timothy Kintu Mike Nsubuga Allan Bakesiga Helen Please Kelsey Stewart Sergio M Navarro African Centre of Excellence in Bioinformatics and Data Intensive Sciences The Infectious Diseases Institute Makerere University P. O. Box 22418 Kampala Uganda The Infectious Diseases Institute Makerere University P. O. Box 22418 Kampala Uganda Faculty of Health Sciences University of Bristol Bristol BS40 5DU UK The African Center of Excellence in Bioinformatics and Data Intensive Sciences Kampala Uganda Makerere University Department of Surgery Kampala Uganda Duke University Department of Surgery Durham NC Oxford University Hospitals NHS Foundation Trust Oxford UK Harris Manchester College University of Oxford Oxford UK Mayo Clinic Department of Obstetrics and Gynecology Rochester MN US Mayo Clinic Department of Surgery Rochester MN US University of Minnesota Department of Surgery Minneapolis MN US

Objectives/Goals: Global surgical education is largely driven by high-income countries (HICs), with curricula not tailored to the needs of low- and middle-income countries (LMICs). This study assessed country-specific needs for global surgical curricula and used generative AI to develop tailored curricula. Methods/Study Population: A curriculum framework was developed using expert opinion. Using a focused needs assessment survey, we evaluated international medical students’ and trainees’ needs for structured global surgery curricula, covering research, education, data and develop tailored curriculum templates for each country, ensuring alignment with the distinct needs of respective LMIC and HIC respondents. The AI-generated curricula were then compared across countries to identify variations in content and focus areas. Results/Anticipated Results: A total of 145 respondents from 18 countries and 6 continents participated, with 94 from LMICs and 51 from HICs. Four countries [Uganda (n = 31), Nigeria (n = 34), the USA (n = 23), and the UK (n = 23)] had more than 10 respondents, with the creation of a country specific global surgery curriculum. Curricula developed by HIC trainees focused on access to resources and infrastructure, future directions of global surgical research, and the role of medical students and early career development with a decreased focus on the history of global surgery. LMIC country-based curriculum focused on introducing the concepts of global surgery, quantifying the burden and epidemiology of surgical disease and had a greater emphasis on case studies and use cases, with decreased focus on resources and collaboration. Discussion/Significance of Impact: The research introduces a “precision education” approach that could help close the surgical education access gap globally. Further pilot and qualitative studies are necessary to validate the feasibility of AI-generated needs-based curricula.

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A secure and efficient anonymous certificateless signcryption for Key Distribution Scheme for Smart Grid

A secure and efficient anonymous certificateless signcryptio...

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Information Technology (ACIT)

作者： Jennifer Batamuliza Damien Hanyurwimfura African center of Excellence in Data Science College of Business and Economics University of Rwanda Kigali Rwanda African center of Excellence in Internet of Things College of Science and Technology University of Rwanda Kigali Rwanda

ISBN: (数字)9781728188553

ISBN: (纸本)9781728188560

Smart Grid uses modern metering electricity and some devices that collect energy data in a real time manner and send the clients usage report of electricity usage to the service provider. The service provider uses the received data for billing the client or other services. Through this smart grid, the daily energy consumption and devices that are being used by home owner can be predicted by the service provider depending on how electricity is consumed. This can lead to security issues security where hackers can easily capture clients data while it's being transferred to the service provider. The hacker can modify the transmitted data and the services provider will receive the wrong data. This paper introduces a key distribution system that is more efficient and secure. Existing identity based encryption and identity based signature schemes for smart grid have key escrow problem. In this paper we introduce a certificateless signcryption for key distribution scheme which is more efficient and secure than the existing schemes. It allows for both decryption and verification by authorized users, provide Key Generation center to only partial key and provide low computation and communication cost compared with existing works. The proposed scheme also achieves key escrow resilience unlike previous works in this field.

关键词： Smart meters Smart grids Public key Protocols Elliptic curves Real-time systems Authentication

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Prediction of blood glucose levels in diabetic and non-diabetic patients using Bi-RNN Transformers

Prediction of blood glucose levels in diabetic and non-diabe...

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IEEE International Conference on Electronics, Computing and Communication Technologies (CONECCT)

作者： Dheeraj Reddy Mudireddy Jatin Thakur Nyirimana Jean Marie Vianney Sanidhya Srivastava Archana Mathur Shalini Joseph Dept. of Information Science Nitte Meenakshi Institute of Technology Bangalore India African Center of Excellence-Data Science University of Rwanda Kigali Rwanda

ISBN: (数字)9798350385922

ISBN: (纸本)9798350385939

Diabetes is a prevalent chronic metabolic disorder with increasing global prevalence, posing significant health challenges. This study explores innovative noninvasive approaches, such as saliva-based glucose monitoring and predictive mathematical models, to accurately estimate blood glucose levels. Leveraging machine learning and deep learning techniques, including Bi-Directional RNNs and Multi-Attention Transformer models, this research proposes a non-invasive method to predict glucose levels in the blood at 30-minute intervals using wearable devices and physiological sensors. By providing continuous and accurate predictions without invasive procedures, this approach aims to improve diabetes management and improve health outcomes for diabetic patients. The study highlights the transformative potential of AI-driven approaches in revolutionizing diabetes care and emphasizes the importance of continuous advancements in non-invasive glucose monitoring in the blood for personalized and effective diabetes management.

关键词： Deep learning Adaptation models Predictive models Transformers Mathematical models Diabetes Glucose

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The dynamic immune behavior of primary and metastatic ovarian carcinoma

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npj Precision Oncology 2025年第1期9卷 1-12页

作者： Stur, Elaine Peng, Fuduan Teng, Pang-Ning Bayraktar, Emine Hu, Min Corvigno, Sara Brown, David J. Lee, Sanghoon Moore, Kathleen N. Bateman, Nicholas W. Darcy, Kathleen M. Maxwell, George L. P. Conrads, Thomas Sahni, Nidhi Vázquez-García, Ignacio Shah, Sohrab P. Celestino, Joseph D. Fleming, Nicole Navin, Nicholas E. Wang, Linghua Sood, Anil K. Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Gynecologic Cancer Center of Excellence The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. Walter Reed National Military Medical Center Bethesda 20889 MD United States Department of Gynecologic Surgery and Obstetrics Uniformed Services University of the Health Sciences Walter Reed National Military Medical Center Bethesda MD United States Department of Genetics The University of Texas MD Anderson Cancer Center Houston TX United States Obstetrics and Gynecology Stephenson Cancer Center Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research Institute Oklahoma City OK United States Women’s Health Integrated Research Center Women’s Service Line Inova Health System Falls Church VA United States Department of Epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Baylor College of Medicine Houston TX United States Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX United States Quantitative and Computational Biosciences Program Baylor College of Medicine Houston TX United States Computational Oncology Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY United States The Halvorsen Center for Computational Oncology Memorial Sloan Kettering Cancer Center Boston MA United States Irving Institute for Cancer Dynamics Columbia University Cambridge 10027 MA United States Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston MA United States The James P. Allison Institute The University of Texas MD Anderson Cancer Center Houston 77030 TX United States The Institute for Data Sc

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation;this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs. © The Author(s) 2025.

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