David A. Braun, MD, PhD
Assistant Professor of Medicine (Medical Oncology), Louis Goodman and Alfred Gilman Yale ScholarCards
About
Research
Overview
How do somatic alterations impact response to immunotherapy?
We integrate genomic, transcriptomic, and immunopathologic analyses with demographic and clinical response data to dissect how tumor genetic features contribute to response or resistance to current immunotherapies, with a focus on immune checkpoint inhibitors (for example, see Braun et al, Nature Medicine, 2020 and Braun et al, JAMA Oncology, 2019)
How does the immune microenvironment impact anti-tumor immunity?
The tumor-immune microenvironment is comprised of heterogeneous cell types that may positively or negatively impact anti-tumor immune responses. Our prior work identified key immune cell populations and cellular interaction circuits that were enriched in advanced kidney cancer (see Braun et al, Cancer Cell, 2021). We now aim to utilize single-cell proteogenomic tools to systematically dissect this complex ecosystem and identify candidate immune cell populations and cellular states that impact response or resistance to immune checkpoint inhibitors. Further, we aim to construct patient-derived model systems to enable a mechanistic understanding of these potential determinants of anti-tumor immunity.
What are the target tumor antigens and what are the characteristics of T cells that recognize them?
The heart of antigen-specific anti-tumor immunity is the interaction between the T cell receptor (TCR) expressed on the surface of tumor-infiltrating T cells (TILs) and the peptide-MHC complex, displayed on a tumor cell. However, in renal cell carcinoma (RCC) and many other cancer types, the important tumor antigens and the T cells that recognize them remain largely unknown. We aim to identify relevant tumor antigens that can ultimately enable innovative “precision” approaches to cancer immunotherapies (for example, see our personalized neoantigen vaccine in RCC, NCT02950766, Co-PIs: Braun, Choueiri, Ott)
Medical Research Interests
Publications
2025
DEVELOPMENT OF EX VIVO PATIENT-DERIVED MODELS TO UNCOVER THE TUMOR-IMMUNE MICROENVIRONMENT IN RENAL CELL CARCINOMA
Kashima S, Gupta R, Moritz V, Sadak K, Walker J, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. DEVELOPMENT OF EX VIVO PATIENT-DERIVED MODELS TO UNCOVER THE TUMOR-IMMUNE MICROENVIRONMENT IN RENAL CELL CARCINOMA. Urologic Oncology Seminars And Original Investigations 2025, 43: 22-23. DOI: 10.1016/j.urolonc.2024.12.057.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionTumor microenvironmentT cellsEnzyme-linked immunosorbent assayFlow cytometryTumor fragmentsTumor samplesCytokine productionImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyCD4+CD25+ regulatory T cellsResection of renal cell carcinomaSurgical resection of renal cell carcinomaCD8+ T cell populationsAnti-PD-1 antibodyMetastatic renal cell carcinomaCD20+ B cellsActivated CD8 T cellsEvaluate T cell activationT cell cytokine productionStudy of renal cell carcinoma831 AXL Receptor Tyrosine Kinase Expression in Metastatic Renal Cell Carcinoma: Insights from the METEOR trial
Laimon Y, Paul M, Jammihal T, Ghandour F, Ahmar N, Simsek B, Matar S, Denize T, Mohanna R, De Oliveira G, Delcea A, Shukla S, Braun D, Sun M, Aftab D, Saad E, Machaalani M, Xie W, Choueiri T, Signoretti S. 831 AXL Receptor Tyrosine Kinase Expression in Metastatic Renal Cell Carcinoma: Insights from the METEOR trial. Laboratory Investigation 2025, 105: 103064. DOI: 10.1016/j.labinv.2024.103064.Peer-Reviewed Original Research796 Tertiary Lymphoid Structures Predict Response to First-Line Nivolumab Therapy in Advanced Renal Cell Carcinoma: Findings from the HCRN GU16-260 Clinical Trial
Ahmar N, Simsek B, Jegede O, Matar S, Savla V, Laimon Y, Mohanna R, De Oliveira G, Sheshdeh A, Delcea A, Paul M, Choueiri T, Xie W, Freeman G, Braun D, Haas N, Hammers H, Bilen M, Stein M, Sosman J, Wu C, McDermott D, Atkins M, Signoretti S. 796 Tertiary Lymphoid Structures Predict Response to First-Line Nivolumab Therapy in Advanced Renal Cell Carcinoma: Findings from the HCRN GU16-260 Clinical Trial. Laboratory Investigation 2025, 105: 103029. DOI: 10.1016/j.labinv.2024.103029.Peer-Reviewed Original ResearchHIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang Q, Braun D, Clauser K, Ramesh V, Shirole N, Duke-Cohan J, Nabilsi N, Kramer N, Forman C, Lippincott I, Klaeger S, Phulphagar K, Chea V, Kim N, Vanasse A, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani E, Stevens J, Lane W, Camp S, Meli K, Pappalardi M, Herbert Z, Qiu X, Cejas P, Long H, Shukla S, Van Allen E, Choueiri T, Churchman L, Abelin J, Gurer C, MacBeath G, Childs R, Carr S, Keskin D, Wu C, Kaelin W. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell 2025 PMID: 40023154, DOI: 10.1016/j.cell.2025.01.046.Peer-Reviewed Original ResearchClear cell renal cell carcinomaCancer immunotherapyAntigen-specific T cell responsesAllogeneic stem cell transplantationEndogenous retrovirusesClear cell renal cell carcinoma patientsLow mutational burdenCell renal cell carcinomaStem cell transplantationT cell responsesRenal cell carcinomaVHL tumor suppressor geneTumor suppressor geneHLA-bound peptidesEndogenous retrovirus expressionNon-ccRCCCell transplantationMutational burdenSpontaneous regressionCell carcinomaT cellsCase reportSuppressor geneHIF transcription factorsImmunotherapyPresence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma.
Hugaboom M, Wirth L, Street K, Ruthen N, Jegede O, Schindler N, Shah V, Zaemes J, El Ahmar N, Matar S, Savla V, Choueiri T, Denize T, West D, McDermott D, Plimack E, Sosman J, Haas N, Stein M, Alter R, Bilen M, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma. Cancer Discovery 2025, of1-of21. PMID: 39992403, DOI: 10.1158/2159-8290.cd-24-0991.Peer-Reviewed Original ResearchTertiary lymphoid structuresRenal cell carcinomaCD8+ T cellsAnti-PD1 monotherapyImmune checkpoint inhibitorsT cellsCell carcinomaLymphoid structuresClinical outcomesClinical response to PD-1 blockadeTreatment of advanced renal cell carcinomaResponse to PD-1 blockadePresence of tertiary lymphoid structuresAdvanced renal cell carcinomaTissue-resident T cellsPD-1 blockadePhase II clinical trialPD-1 pathwayCheckpoint inhibitorsICI resistancePD-1Responding patientsTumor microenvironmentTherapeutic responseTissue-residentLocal definitive therapy (LDT) utilization patterns and outcomes in chromophobe renal cell carcinoma (chRCC) with metachronous metastasis: A multi-institution study.
Dizman N, Doshi S, Knezevic A, Feinaj A, Sayegh N, Hobeika C, Alaghehbandan R, Rives H, Zengin Z, Braun D, Zibelman M, McGregor B, Hammers H, Ged Y, Ornstein M, Msaouel P, Hahn A, Voss M. Local definitive therapy (LDT) utilization patterns and outcomes in chromophobe renal cell carcinoma (chRCC) with metachronous metastasis: A multi-institution study. Journal Of Clinical Oncology 2025, 43: 503-503. DOI: 10.1200/jco.2025.43.5_suppl.503.Peer-Reviewed Original ResearchLocal definitive therapySarcomatoid dedifferentiationMetachronous metastasesSystemic treatmentST cohortDuration of disease controlChromophobe renal cell carcinomaTreatment characteristics of patientsMetastatic disease diagnosisSingle-organ metastasisTreatment-free intervalTreatment-free survivalKaplan-Meier methodRenal cell carcinomaFisher's exact testCharacteristics of patientsMulti-institutional studyWilcoxon rank sum testRank sum testMetastatic sitesSurgical resectionDefinitive therapyRare subtypeMedian intervalCell carcinomaA comprehensive evaluation of gene expression-based signatures for detecting tertiary lymphoid structures (TLS) in metastatic renal cell carcinoma (mRCC).
Saad E, El Ahmar N, Simsek B, Jegede O, Matar S, Mohanna R, Yekeduz E, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Van Allen E, Choueiri T, Atkins M, Signoretti S, Braun D. A comprehensive evaluation of gene expression-based signatures for detecting tertiary lymphoid structures (TLS) in metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2025, 43: 591-591. DOI: 10.1200/jco.2025.43.5_suppl.591.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaMature tertiary lymphoid structuresTertiary lymphoid structuresTLS signatureArea under the receiver operating characteristicSignature scoreGene set variation analysisExpression-based signaturesCD8 densityStaining of tumor sectionsTertiary lymphoid structure densityResponse to immunotherapyTreatment naive patientsGene signature scoresGene expression-based signaturesRenal cell carcinomaSpearman correlationGene expression signaturesReceiver operating characteristicPrimary tumorAlternative diagnostic toolCell carcinomaTumor sectionsLymphoid structuresLymphoid aggregatesINTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC).
Motzer R, Braun D, Powles T, Gurney H, Fong L, George D, Haas N, McDermott D, Shuch B, Meehan R, Posadas T, Wu S, Elfiky A, Choueiri T. INTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: tps610-tps610. DOI: 10.1200/jco.2025.43.5_suppl.tps610.Peer-Reviewed Original ResearchRenal cell carcinomaWeeks prior to randomizationAdverse eventsTumor-specific T-cell activationResection of metastatic lesionsAdjuvant treatment of patientsIncreased risk of recurrenceStage III/IV melanomaImmune checkpoint inhibitorsDisease-free survivalMetastasis-free survivalPhase 2 trialRisk of recurrenceDouble-blind studyT cell activationTreatment of patientsNovel combination strategiesDose of treatmentAdjuvant pembrolizumabAdjuvant settingCheckpoint inhibitorsPapillary histologyPD-1Sarcomatoid featuresMetastatic lesionsCabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): Final results of COSMIC-313.
Albiges L, Motzer R, Trevino S, Kanesvaran R, Centkowski P, Reimers M, Sade J, Pouessel D, Biscaldi E, Esteban E, Arranz Arija J, Tykodi S, Ma H, Zhou L, Van Kooten Losio M, Simmons A, Rangwala F, Braun D, Choueiri T, Powles T. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): Final results of COSMIC-313. Journal Of Clinical Oncology 2025, 43: 438-438. DOI: 10.1200/jco.2025.43.5_suppl.438.Peer-Reviewed Original ResearchAdvanced renal cell carcinomaPoor-risk advanced renal cell carcinomaTreatment-emergent AEPrimary endpointSecondary endpointsMacrophage abundanceUntreated advanced renal cell carcinomaPresence of visceral metastasesBlinded independent central reviewExploratory biomarker analysesIMDC risk groupsPD-L1 levelsBiomarker analysisIndependent central reviewEndpoint of OSFirst-line treatmentRenal cell carcinomaBaseline sumIMDC intermediateIMDC riskVisceral metastasesPD-L1ITT populationOS outcomesIncidence of PDComprehensive proteomic profiling of plasma samples associated with response or resistance to immune checkpoint inhibitors (ICI) in patients with renal cell carcinoma (RCC).
Kashima S, Xu W, Canniff J, Saliby R, Sun M, Lee G, Machaalani M, Signoretti S, McGregor B, McKay R, Choueiri T, Braun D. Comprehensive proteomic profiling of plasma samples associated with response or resistance to immune checkpoint inhibitors (ICI) in patients with renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: 562-562. DOI: 10.1200/jco.2025.43.5_suppl.562.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaRenal cell carcinoma patientsICI-based therapyNon-respondersPatients treated with ICI monotherapyResistance to immune checkpoint inhibitorsHLA-BICI respondersAdvanced renal cell carcinomaImmune cells to tumorsTGF-B pathwayTreatment evolutionCells to tumorsSustained immune activationPlasma samplesProfiling of plasma samplesCornerstone of treatmentPaired samplesPlasma proteomic analysisAssociated with responseAnti-tumor inflammationICI monotherapyInvestigated plasma proteinsCheckpoint inhibitors
Clinical Trials
Current Trials
A Phase 1a Open-Label, Dose-Escalation, and a Phase 2 Study to Investigate the Safety, PK, PD, and Clinical Activity of ST-067 Administered Subcutaneously as Monotherapy in Patients With Relapsed or Refractory Solid Tumors
HIC ID2000030299RoleSub InvestigatorPrimary Completion Date06/30/2025Recruiting Participants
Academic Achievements & Community Involvement
Clinical Care
Overview
David A. Braun, MD, PhD, specializes in medical oncology and hematology, focusing on the treatment of kidney cancers.
As an assistant professor of medicine at Yale School of Medicine, Dr. Braun is dedicated to advancing the understanding and application of immune therapies in kidney cancer.
Immune therapy is a treatment that helps the body’s own defense system, the immune system, fight cancer. Normally, the immune system might not recognize cancer cells because they can disguise themselves. Immune therapy works by removing the "brakes" that prevent the immune system from attacking cancer, allowing it to better target and destroy cancer cells.
Dr. Braun’s research involves exploring how the environment around kidney cancer cells affects treatment and finding specific targets on cancer cells to develop personalized therapies for diseases like renal cell carcinoma.
Dr. Braun received his doctoral degree in computational biology from New York University and his medical degree from the Icahn School of Medicine at Mount Sinai. He completed his residency at Brigham and Women's Hospital and a fellowship in adult oncology through the Dana-Farber/Partners Cancer Care program.
Clinical Specialties
Fact Sheets
Kidney Cancer
Learn More on Yale MedicineUrologic Cancers
Learn More on Yale MedicineDiagnosing Kidney Disease
Learn More on Yale MedicineDiagnosing Lupus Nephritis
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Board Certifications
Medical Oncology
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 2020
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 2016
Yale Medicine News
News
News
- April 17, 2025Source: Google Research
Teaching machines the language of biology: Scaling large language models for next-generation single-cell analysis
- April 01, 2025
YCC Publications 2025
- March 14, 2025Source: WFSB Eyewitness News (with Dr. David Braun)
Making a Mark: Local Vaccine Trial Taking Personal Approach to Treating Kidney Cancer
- March 14, 2025Source: WTNH News 8 (with Dr. David Braun)
Therapeutic vaccine for kidney cancer provided positive results in study
Get In Touch
Contacts
Yale School of Medicine
333 Cedar St, PO Box 208028
New Haven, CT 06520
United States
Administrative Support
Locations
BraunLab
Lab
300 George Street, Fl 6th Floor, Ste Suite 6400
New Haven, CT 06511
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