About

Robert H. Vonderheide, MD, DPhil, is the John H. Glick Abramson Cancer Center Professor at the University of Pennsylvania. He serves as an Attending Physician at the Hospital of the University of Pennsylvania and is an Investigator at the Abramson Family Cancer Research Institute. He is also the Director of the Abramson Cancer Center and the Abramson Family Cancer Research Institute, as well as Vice Dean of Cancer Programs at the Perelman School of Medicine. His research combines basic and clinical investigation efforts to advance the understanding of tumor immunology and develop novel immunotherapies for cancer. His chief hypothesis emphasizes that successful tumor immunotherapy approaches need to optimize target antigens, repair host immuno-incompetence in antigen presentation and T cell function, and circumvent immuno-suppressive factors within the tumor microenvironment. His basic research includes deciphering the immunobiology of genetically engineered mouse models of cancer, focusing on immune surveillance and the tumor microenvironment, particularly in pancreatic cancer, breast cancer, and melanoma. His translational work tests novel approaches such as vaccines, antibodies, and adoptive T cell therapies for patients with melanoma, pancreatic cancer, and other cancers. Dr. Vonderheide has studied universal tumor antigens, immune effects of radiation, and immune modulatory pathways involving CD40, GM-CSF, PD-1, CTLA-4, and CD25. His work has been published in high-impact journals including Nature, Science, Cell, and the New England Journal of Medicine. He leads a laboratory team that includes various researchers and clinicians dedicated to advancing cancer immunotherapy.

Research topics

• Medicine
• Internal medicine
• Biology
• Immunology
• Cancer research

Selected publications

• Author response: Repression of PRMT activities sensitize human homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment

  2026-02-03

  peer-reviewOpen access
  PublisherDOI

• Supplementary Figure 1 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 1. Anti-CD40/ICB immunotherapy slows tumor growth in a CD4+ T cell-dependent, but CD8+ T cell- and NK1.1 cell-independent manner.</p>

  PublisherOA PDFDOI

• Supplementary Figure 2 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 2. Knockout tumor cell lines lack expression of antigen presentation molecules.</p>

  PublisherOA PDFDOI

• Supplementary Figure 5 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 5. Immunotherapy-induced rejection of V6K is not mediated by TNF-α or IFN-γ.</p>

  PublisherOA PDFDOI

• Data from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <div>Abstract<p>Low or absent expression of MHC on tumor cells is a presumed mechanism of resistance to immunotherapy, but evidence for this has largely been indirect. Likewise, whether immunotherapy can be effective without tumor MHC expression is also poorly understood. Using genetically engineered mouse tumor cells expressing the model neoantigen ovalbumin, we found that MHC class I–deficient tumor cells, but not MHC class I–sufficient tumor cells, grew progressively when injected subcutaneously into syngeneic C57BL/6 mice. However, combination immunotherapy using agonistic anti-CD40 and dual immune checkpoint blockade (anti–PD-1 and anti–CTLA-4) was equally effective against tumors that did not express the MHC class I H-2K<sup>b</sup> allele, MHC class II, or IFNγ receptor across multiple pancreatic tumor lines (regardless of ovalbumin). Moreover, CD4<sup>+</sup> T cells, but not CD8<sup>+</sup> T cells or perforin, were necessary to mediate immunotherapeutic responses. We excluded a role for CD4<sup>+</sup> T cell–instructed macrophage-mediated tumor cell death but observed reprogramming of MHC class II–expressing stromal cells within the tumor after anti-CD40/ICB treatment. These data indicate that cancer immune surveillance by T cells does not absolutely require tumor-expressed MHC class I nor CD8<sup>+</sup> T cells but instead can facilitate a clinically relevant remodeling of endothelial cells, further underscoring tumor-extrinsic roles for CD4<sup>+</sup> T cells as mediators of tumor rejection and durable immune memory.</p></div>

  PublisherDOI

• Supplementary Figure 6 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 6. Anti-CD40/ICB-induced rejection of V6K is not mediated by macrophages or myeloid cells.</p>

  PublisherOA PDFDOI

• Supplementary Figure 3 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 3. Memory immune cells reject secondary tumors.</p>

  PublisherOA PDFDOI

• Ten-year patterns of women participating in treatment clinical trials for cancer

  Preventive Oncology & Epidemiology · 2026-01-10

  articleOpen accessSenior authorCorresponding

  BackgroundAchieving representative participation of women in clinical trials has been challenging. To understand the impact of federal policies aimed at addressing this issue, we analyzed women’s participation in cancer trials at our institution.MethodsIn this retrospective observational study, we quantified participation of women across cancer treatment clinical trials at the Abramson Cancer Center (ACC) from 2012-2022. Deidentified data were available from 9,639 women and 8,225 men aged > = 18 years with cancer/pre-cancer and enrolled in a cancer treatment clinical trial. Cancers largely affecting one sex were excluded. Participation rates for each cancer were compared to sex incidence rates nationally and in our catchment area.ResultsThe percentage of women participating in cancer studies at ACC was 54% +/- 5.7% (mean +/- SD, range 43.3% to 66.0%). Women participation was similar to national incidence for all cancers except ENT and neurologic (by ≥5%), and thyroid (by ≤5%). Compared to our catchment area, women participated more in neurologic and less in pancreas and thyroid; compared to ACC patients, less in liver.ConclusionsWhen subdivided by cancer, over 10 years and a pandemic, women were equitably represented in clinical trials at our cancer center compared to all benchmarks, achieving the goals of federal mandates and our institution.

  PublisherDOI

• Clinical and translational results from a phase 1 trial of gemcitabine/nab-paclitaxel with nivolumab/ipilimumab or hydroxychloroquine/ipilimumab in untreated metastatic pancreatic adenocarcinoma

  Journal for ImmunoTherapy of Cancer · 2026-01-01

  articleOpen accessSenior author

  Background Patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) often respond to cytotoxic therapy, but early disease progression is typical. Responses to immunotherapy alone are rare. Recent advances in chemoimmunotherapy combinations offer promise. We report results from cohorts A and B of REVOLUTION, an adaptive platform trial designed to evaluate the safety and antitumor activity of chemoimmunotherapy combinations in untreated mPDAC. Methods REVOLUTION ( NCT04787991 ) is an open-label, exploratory platform trial. Patients were assigned to enrolling cohorts in a non-randomized fashion. All patients received gemcitabine (1,000 mg/m 2 ), nab-paclitaxel (125 mg/m 2 ), and two doses of ipilimumab (1 mg/kg), administered intravenously. In addition, cohort A received nivolumab (360 mg intravenously every 3 weeks) and cohort B received hydroxychloroquine (600 mg orally two times a day). The primary endpoint was safety. Secondary endpoints included objective response rate (ORR), disease control rate, duration of response, progression-free survival, and overall survival (OS). Exploratory endpoints included pharmacodynamic changes and associations between biomarkers and clinical outcomes. Results Both cohorts enrolled 15 patients. Grade 3–4 treatment-related adverse events occurred in 60% and 53% of patients in cohorts A and B, respectively. One grade 5 event occurred in cohort B, which exhibited more frequent dose modifications and non-compliance. Cohort A demonstrated an ORR of 33% (5/15) and a 12-month OS rate of 65.5% (95% CI 35.7% to 84.0%), with higher baseline levels of programmed cell death protein-1 (PD-1) + CD39 + central memory CD4 + T cells associated with prolonged survival. Cohort B demonstrated an ORR of 40% (6/15) and a 12-month OS rate of 53.9% (95% CI 24.3% to 76.3%). Cohort A showed increases in activated and proliferating CD4 + and CD8 + T cells, regulatory T cells, and circulating soluble PD-1 and Th1-associated cytokines. Cohort B exhibited delayed but sustained increases in activated CD4 + T cells and pharmacodynamic evidence of autophagy inhibition. Conclusions REVOLUTION cohorts A and B demonstrated encouraging antitumor activity in patients with mPDAC. In cohort B, hydroxychloroquine-related tolerability issues contributed to early discontinuations and reduced drug exposure. These findings highlight the potential and limitations of current chemoimmunotherapy approaches. Although neither cohort will be expanded, the results reinforce the continued promise of chemoimmunotherapy in mPDAC and the importance of refining these strategies.

  PublisherOA PDFDOI

• Supplementary Figure 7 from CD4<sup>+</sup> T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming

  2026-01-08

  articleOpen access

  <p>Supplementary Figure 7. Stromal cell gating for flow cytometry.</p>

  PublisherOA PDFDOI

Recent grants

• Radiation and checkpoint blockade for cancer immune therapy

  NIH · $18.3M · 2017–2024

• NIH Grant R01CA158186

  NIH · $1.6M · 2016

• NIH Grant R01CA169123

  NIH · $3.1M · 2018

• Developmental Research Program

  NIH · $17.8M · 2021

• Radiobiology and Imaging Program

  NIH · $93.0M · 1997–2027

Frequent coauthors

• Ben Z. Stanger

  University of Pennsylvania

  182 shared

• Katelyn T. Byrne

  162 shared

• Carl H. June

  Parker Institute for Cancer Immunotherapy

  150 shared

• E. John Wherry

  University of Pennsylvania

  130 shared

• Gregory L. Beatty

  University of Pennsylvania

  129 shared

• Joachim L. Schultze

  University of Bonn

  125 shared

• Rebecca A. Evans

  University of Warwick

  118 shared

• Andrew J. Rech

  117 shared

Labs

• Vonderheide LaboratoryPI