About

Dr. Robert M. Prins is a tumor immunologist and Professor with dual appointments in the departments of Neurosurgery and Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA. He received his B.S. degree in Kinesiology and his Master’s degree in Physiological Science from UCLA. He then earned a PhD in Anatomy and Immunology from the Medical College of Virginia in 2001. Following his doctoral studies, he completed post-doctoral fellowships at Cedars-Sinai Neurosurgical Institute and UCLA Division of Neurosurgery, focusing on tumor immunology. Dr. Prins joined UCLA’s faculty as an Assistant Professor in 2006, was promoted to Associate Professor in 2010, and became a full Professor in 2017. He currently directs the Brain Tumor Immunotherapy Research Lab and oversees the training of multiple graduate students, medical students, residents, and hematology/oncology fellows. His research focuses on tumor immunology, particularly in the context of brain tumors, and he is actively involved in advancing immunotherapeutic strategies for cancer treatment.

Research topics

• Medicine
• Internal medicine
• Cancer research
• Pathology
• Immunology
• Oncology
• Biology
• Surgery
• Cell biology

Selected publications

• Predictable clonal hierarchies from restricted progenitors provide a framework for cell type-specific therapies in glioblastoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-23 · 1 citations

  articleOpen access

  Extensive molecular profiling has revealed profound heterogeneity in glioblastoma (GBM), yet how cellular lineages organize over time to govern tumor propagation and therapeutic response remains poorly understood. Existing single-cell approaches define transcriptional states but provide limited insight into how clonal dynamics shape functional tumor behavior. Here, we integrate high-complexity combinatorial DNA barcoding with single-cell transcriptomics in direct-from-patient IDH1-wild-type GBM, enabling lineage-resolved mapping of progenitor organization in a human microenvironmental context. Across 235,155 malignant cells from nine tumors, clonal relationships form reproducible lineage tracks in which distinct progenitor populations give rise to specific differentiated cell types, revealing that tumor growth is sustained by multiple non-redundant progenitors rather than a single dominant population. These progenitors exhibit distinct propensities for self-renewal, fate restriction, and cross-compartment interactions, collectively accounting for the full spectrum of tumor states. Using this lineage-resolved framework, we identify complementary drug targets in distinct progenitor compartments and demonstrate that hierarchy-informed combination therapies disrupt progenitor-progenitor interactions and reshape lineage output. These findings move beyond descriptive heterogeneity to define functional logic underlying GBM propagation and establish a generalizable framework for rational, cell type-specific combinatorial therapies.

  PublisherOA PDFDOI

• 119 A Novel Radiographic Signature of Immune Exclusion in Brain Metastases

  Neurosurgery · 2026-03-26

  article
  PublisherDOI

• Therapeutic efficacy of dendritic cell vaccination in a novel syngeneic mouse model of diffuse hemispheric glioma, H3 G34-mutant

  Journal of Neuro-Oncology · 2026-04-01

  articleOpen access

  The prognosis for pediatric high-grade gliomas associated with mutations in the H3-3A gene is very poor. To investigate whether tumor lysate-pulsed dendritic cells (DC) together with checkpoint blockade might be a potential treatment modality for diffuse hemispheric glioma H3 G34-mutant (DHG), we have developed a novel syngeneic mouse model. We used the RCAS/tv-A system to target the expression of H3G34R and PDGFβ and knock out p53 in neural progenitors in C57BL/6 neonatal mice. Three independent cell lines were obtained that expressed transcripts associated with oligodendrocyte and interneuron lineages. Lethal tumor developed following intracranial injection. Two cycles of DC vaccination with PD-1 blockade decreased tumor burden and increased survival. In treatment resistant tumors we found higher expression of several genes involved in remodeling the extracellular matrix compared with tumors from untreated animals, suggesting a causal link to resistance to immunotherapy in this tumor model. Immunotherapy involving autologous dendritic cells pulsed with tumor lysate and combined with anti-PD-1 antibody might be an effective treatment for DHG. Treatment failure in our tumor model is associated with increased expression of genes implicated in remodeling extracellular matrix in the tumor microenvironment.

  PublisherOA PDFDOI

• Abstract 1080: Development of a murine leptomeningeal disease model for a point-of-care cerebrospinal fluid liquid biopsy assay

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Background: Leptomeningeal disease (LMD), the metastatic dissemination of cancer cells to the leptomeninges and cerebrospinal fluid (CSF), is a devastating complication of cancer. LMD occurs most commonly in advanced melanoma, lung, and breast cancers, and typically portends a poor prognosis that is accompanied by rapid neurological decline. Diagnosis and disease monitoring has been historically challenging. Prior work by our colleagues has led to the development of a barcode-style rapid, semi-quantitative lateral flow assay (LFA) able to detect MCF-7 breast cancer cells in artificial CSF using an epithelial marker. Here, we present murine models of LMD developed to further refine the assay and test its detection limit in an in vivo setting. Methods: Two brain-tropic murine cancer lines previously generated by serial in vivo intracarotid injections, B16-BrM melanoma and LLC-LeptoM lung carcinoma, were engineered to stably express mCherry and secreted Gaussia luciferase (sGluc) via lentiviral transduction. Pure populations were isolated by fluorescence-activated cell sorting, and bioluminescence signal was evaluated in vitro using cultured supernatant at various cell concentrations. For in vivo studies, 1000 parental or mCherry-sGluc cells were stereotaxically injected into the right lateral ventricle of syngeneic C57BL/6 mice at 8-10 weeks of age. CSF was collected terminally via cisterna magna puncture on days 1, 5, 9, and 13 post-implantation. Tumor burden was assessed using bioluminescence and flow cytometry on CSF. Murine brains were collected and processed for histological analyses. Results: Bioluminescence signal was detectable in cultured supernatant from both B16-BrM and LLC-LeptoM cells, even in concentrations less than 10 cells per ml. When adopted into the in vivo LMD model, mice began to display clinical decline starting around day 12 post-implantation. Histological analysis demonstrated tumor cell clusters sequestered in the ventricular space. Bioluminescence signal was detectable from just 1 ul of mouse CSF in animals injected with mCherry-sGluc cells, compared to those injected with parental cells or with no injection. On day 13 post-implantation, bioluminescence signal was saturated in about half of the experimental cohort. In most cases, bioluminescence was detected in CSF even when mCherry+ cells were not detected on flow cytometry. Conclusion: We have established a murine LMD model that allows for highly sensitive detection of tumor burden via liquid biopsy of CSF. Further studies evaluating tumor burden kinetics and the performance of the point-of-care LFA on mouse and human CSF are ongoing. The success of this work may revolutionize the diagnosis and management of LMD. Citation Format: Eileen Shiuan, Jorge Salcedo-Sifuentes, Leilani Pradis, Trinh Phan, Sonia Su, Martin Shum, Daniel T. Kamei, Won Kim, Robert M. Prins. Development of a murine leptomeningeal disease model for a point-of-care cerebrospinal fluid liquid biopsy assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1080.

  PublisherDOI

• 1200 Developing an Autologous Human Organoid Model to Evaluate Response to Immunotherapy in Glioblastoma

  Neurosurgery · 2026-03-26

  article
  PublisherDOI

• Abstract A003: Antigen-specific CD8+ T cells remodel the glioblastoma tumor microenvironment

  Cancer Immunology Research · 2026-02-18

  articleSenior author

  Abstract Glioblastoma (GBM) is the most aggressive and most common form of brain cancer. The current standard of care, surgery and chemoradiation, fails to have durable clinical benefit, resulting in a 90% recurrence rate and poor survival in patients. The clinical success of immune checkpoint blockade (ICB) in several cancers has motivated their application in GBM. However, the abundant myeloid immunosuppression and low T cell infiltration in the GBM tumor microenvironment (TME) pose a significant challenge. To test this in an immunocompetent murine model, we developed the Mosaic Analysis with Dual-Recombinase mediated cassette exchange (MADR) model expressing murine epidermal growth factor receptor variant III (mEGFRvIII), loss-of-function mutations in PTEN and CDKN2A, and a minimal self-tumor antigen, hgp100. Immune assessments of orthotopic MADR-hgp100 gliomas suggest that the scarcity of tumor-infiltrating lymphocytes critically limits anti-tumor immune responses. To evaluate whether antigen-specific T cell expansion in these tumors was critical for anti-tumor immunity, we tested a novel mRNA lipid nanoparticle (mRNA-LNP) vaccine platform to drive antigen-specific T cell expansion in our MADR-hgp100 model. We utilized the adoptive transfer of small numbers of Pmel-1 T cells (∼500 cells) as a model system to track antigen-specific CD8+ T cell expansion, infiltration, and anti-tumor activity. Tumor-bearing C57BL/6 mice received naïve pmel T cells and were subsequently immunized with the gp-100-encoding mRNA-LNP. We found that vaccine-treated mice had extended survival compared to the untreated mice, correlating to a notable expansion of antigen-specific and endogenous T cells in the spleen, tumor-draining lymph nodes, and brain. Our findings highlight the efficacy of an mRNA-LNP vaccine platform in remodeling the immunosuppressive TME and boosting anti-tumor immune responses in GBM, thereby achieving a greater therapeutic effect. Citation Format: Madeline C. Ho, Julio C. Sanchez, Marissa S. Pioso, Marissa Li, Isabelle Phan, Petra Youssef, Hailey Lee, Khalid Rashid, Caius Radu, Robert M. Prins. Antigen-specific CD8+ T cells remodel the glioblastoma tumor microenvironment [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A003.

  PublisherDOI

• 59546 Alternative Splice Variant-Targeted Dendritic Cell Therapy Generates a Systemic Oligoclonal Anti-Tumor Cytotoxic T Cell Response in Diffuse Hemispheric Glioma, H3 G34-Mutant: Early Findings From a First-In-Human Clinical Trial

  Neurosurgery · 2026-03-26

  article
  PublisherDOI

• A human tumor-immune organoid model of glioblastoma

  Cell Reports · 2026-01-01 · 8 citations

  articleOpen access

  A major obstacle to identifying effective therapies for the aggressive brain tumor glioblastoma is the lack of human-specific, immunocompetent models that reflect the human tumor microenvironment. To address this, we developed the immune-human organoid tumor transplantation (iHOTT) model, an autologous co-culture platform that integrates patient-derived tumor cells and matched peripheral blood mononuclear cells within human cortical organoids to enable the study of patient-specific immune responses and tumor-immune interactions. This platform preserves tumor and immune populations, immune signaling, and cell-cell interactions observed in patient tumors. Treatment of iHOTT with pembrolizumab, a checkpoint inhibitor, mirrors cell-type shifts and cell-cell interactions observed in patients. T cell receptor (TCR) sequencing further reveals pembrolizumab-driven expansion of stem-like CD4 T cell clonotypes exhibiting patient-specific repertoires. These findings establish iHOTT as a physiologically relevant platform for exploring autologous tumor-immune interactions and underscore the need for antigen-targeted strategies to enhance immunotherapy in glioblastoma.

  PublisherDOI

• Abstract A069: Oncogenic EGFR signaling promotes intratumoral infiltration of antigen-specific T cells and myeloid cells while impeding T cell function in a mouse model of glioma

  Cancer Immunology Research · 2026-02-18

  articleSenior author

  Abstract Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Despite the transformative impact of immunotherapies in other cancers, clinical trials in GBM have yielded only modest improvements in median overall survival. Oncogenic EGFR signaling, present in approximately 50% of GBMs, is associated with suppression of adaptive immunity, potentially mediated by tumor-associated macrophages (TAMs) that maintain a chronic interferon-response state. To investigate how EGFR signaling shapes the tumor immune microenvironment (TIME), we leveraged the MADR-mEGFRvIII (MADR) model, which expresses the constitutively active EGFR variant EGFRvIII under a tetracycline-off system. Immune checkpoint blockade is ineffective in this model due to poor intratumoral T cell infiltration, closely mirroring human GBM. Previous data demonstrated that short-term genetic EGFR ablation with doxycycline (dox) increases intratumoral CD4+ and CD8+ T cell infiltration in MADR tumors. We also previously showed that tumor-intrinsic oncogenic EGFR signaling reprograms TAMs to an inflammatory state, which, when chronically sustained, may impair T cell function. Together, these findings suggest that EGFR inhibition could be combined with T cell-based immunotherapy to recondition the TIME and enhance adaptive immunity. Thus, to study T cell trafficking and function in the context of EGFRvIII signaling, we used hgp100-specific Pmel-1 CD8+ T cells for adoptive cell transfer (ACT) in C57BL/6 mice implanted with hgp100-expressing MADR tumor cells. Mice received daily treatment with dox (20 mg/kg) or saline beginning day 9 post-implantation, followed by i.p. administration of 5.0x105 pre-activated Pmel-1 T cells on day 13. Tumor-infiltrating leukocytes (TILs) were isolated for flow cytometric analysis from tumor-bearing brain hemispheres on day 20. We hypothesized that initiating genetic EGFR ablation prior to ACT would enhance T cell infiltration, activation, and reduce TAM abundance in the TIME. However, we observed a marked increase in Pmel-1 T cell (Thy1.1+) infiltration in saline-treated tumors compared to EGFR-ablated tumors. However, in the EGFR-ablated setting, a greater proportion of infiltrating Pmel-1 T cells expressed CD25, CXCR3, and CCR2. EGFR ablation also increased the proportion of microglia (CD45loCD11b+) while decreasing the proportion of infiltrating CD45hiCD11b+ cells. These findings suggest a dual role for oncogenic EGFR signaling, where it may promote recruitment of both antigen-specific T cells and immunosuppressive myeloid cells, while dynamically shaping T-cell activation states. These data provide unique insight into the molecular mechanisms driving EGFR-influenced T cell trafficking and provide a compelling rationale for temporally optimizing EGFR inhibition and ACT. Citation Format: Marissa Li, Marissa S. Pioso, Julio C. Sanchez, Katie B. Grausam, Joshua J. Breunig, David A. Nathanson, Robert M. Prins. Oncogenic EGFR signaling promotes intratumoral infiltration of antigen-specific T cells and myeloid cells while impeding T cell function in a mouse model of glioma [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A069.

  PublisherDOI

• A Human Tumor-Immune Organoid Model of Glioblastoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-20 · 3 citations

  preprintOpen access

  A major obstacle to identifying effective therapies for the aggressive brain tumor glioblastoma is the lack of human-specific, immunocompetent models that reflect the human tumor microenvironment. To address this, we developed the immune-Human Organoid Tumor Transplantation (iHOTT) model. This is an autologous co-culture platform that integrates patient-derived tumor cells and matched peripheral blood mononuclear cells (PBMCs) within human cortical organoids, enabling the study of the patient-specific immune response to the tumor and tumor-immune interactions. This platform preserves tumor and immune populations, immune signaling, and cell-cell interactions observed in patient tumors. Treatment of iHOTT with pembrolizumab, a checkpoint inhibitor, mirrored cell type shifts and cell interactions observed in patients. TCR sequencing further revealed pembrolizumab-driven expansion of stem-like CD4-T-cell clonotypes exhibiting patient-specific repertoires. These findings establish iHOTT as a physiologically relevant platform for exploring autologous tumor-immune interactions and underscore the critical need for antigen-targeted strategies to enhance immunotherapy in glioblastoma.

  PublisherDOI

Recent grants

• UCLA SPORE in Brain Cancer

  NIH · $35.6M · 2017–2027

• NIH Grant K01CA111402

  NIH · $705k · 2012

• NIH Grant R01CA123396

  NIH · $939k · 2012

• Identification and cloning of neoantigen-specific T cells for GBM immunotherapy

  NIH · $2.0M · 2019–2025

• NIH Grant R01CA154256

  NIH · $1.9M · 2016

Frequent coauthors

• Linda M. Liau

  318 shared

• Timothy F. Cloughesy

  University of California, Los Angeles

  198 shared

• Horacio Soto

  181 shared

• Richard G. Everson

  Harbor–UCLA Medical Center

  164 shared

• David A. Nathanson

  162 shared

• Paul S. Mischel

  Stanford University

  115 shared

• David Akhavan

  The University of Kansas Cancer Center

  109 shared

• Patrick Y. Wen

  96 shared

Labs

• Brain Tumor Immunotherapy Research LabPI

Education

• Ph.D., Anatomy and Immunology

  Virginia Commonwealth University School of Medicine

  2001

• M.S., Physiological Science

  UCLA Graduate Medical Education

  1996

• B.S., Kinesiology

  UCLA Life Sciences

  1992