About

Xiaowei Xu, MD, PhD, is the Founders Professor in Pathology and Laboratory Medicine at the University of Pennsylvania Perelman School of Medicine. He serves as an Attending Physician in the Department of Pathology and Laboratory Medicine and is a member of the Abramson Cancer Center. His research expertise includes developing CAR gamma delta T cell and extracellular vesicle-based immunotherapies for melanoma and other skin conditions. His clinical expertise encompasses dermatopathology, pigmented lesions, and vasculitis. Dr. Xu has contributed to the understanding of tumor immunosuppression mechanisms, including the role of exosomal PD-L1 in mediating tumor immune evasion, and has worked on signaling pathways involved in acquired drug resistance in melanoma. His work involves engineering immune cells and extracellular vesicles to target tumors and modulate immune responses, with a focus on translational and clinical research in cancer immunotherapy.

Research topics

• Biology
• Cell biology
• Information Retrieval
• Biochemistry
• Cancer research
• Computer Science
• Dermatology
• Medical physics
• Immunology
• Pathology
• Chemistry
• Computational biology
• Genetics
• Materials science
• Evolutionary biology
• Internal medicine
• Medicine

Selected publications

• <scp>PTRF</scp> Confers Melanoma‐Acquired Drug Resistance Through the Upregulation of <scp>EGFR</scp>

  Cell Proliferation · 2025-07-31 · 4 citations

  articleOpen accessCorresponding

  Melanoma is the most serious type of skin cancer. About half of all melanomas have activating BRAF mutations. Targeted therapy for malignant melanoma with BRAF inhibitor (BRAFi) or its combination with MEK inhibitor (MEKi) improves the clinical outcomes of patients, but resistance develops invariably. The underlying mechanisms remain incompletely understood. Here, we show that caveolae number is increased in both BRAFi and BRAFi + MEKi-resistant melanoma cells, and the expression of the critical caveolae component PTRF is significantly upregulated in drug-resistant melanoma cell lines and tumour tissues. Knockdown of PTRF in drug-resistant cells reduces proliferation with increased apoptosis, whereas ectopic expression of PTRF confers resistance on parental cells to BRAFi or BRAFi + MEKi. On the contrary, the knockdown of PTRF in parental cells reduces their ability to acquire drug resistance induced by BRAFi treatment. Interestingly, we find that the expression of EGFR is increased along with PTRF and caveolin-1 in drug-resistant cells and in PTRF transduced parental cells, whereas knockdown of PTRF results in down-regulation of EGFR expression and attenuates drug resistance of parental cells induced by PTRF expression. Together, these results suggest that PTRF contributes to therapy resistance through upregulating EGFR in melanoma cells.

  PublisherOA PDFDOI

• DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity

  Molecular Therapy · 2025-12-11

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Droplet Squeeze Microfluidic Platform for Generating Extracellular Vesicle Hybrids for Drug Delivery

  Small · 2025-08-07 · 8 citations

  articleOpen access

  Extracellular vesicles (EVs) are emerging as versatile drug delivery systems due to their intrinsic biocompatibility and targeting capabilities. However, EV integrity and efficient drug loading challenges hinder their clinical translation. To address these limitations, hybrid systems integrating lipid nanoparticles (LNPs) with EVs have gained attention for their potential in targeted and combinatorial drug delivery. This study presents a robust microfluidic approach for the scalable generation of drug-loaded EV-LNP hybrids (EV hybrids). The method facilitates controlled fusion between EVs and LNPs by utilizing a droplet-mediated squeezing mechanism. Lipid composition and microfluidic parameters are optimized for the fusion of EVs and LNPs and determined physicochemical and functional characterizations of the EV hybrids. In vitro studies demonstrate that EV hybrids exhibit enhanced targeting efficiency. Moreover, small-molecule therapeutics are successfully encapsulated within EV hybrids, significantly improving cytotoxic efficacy against melanoma in 2D and 3D culture models compared to drug-loaded EVs or LNPs alone. The work introduces a scalable, minimally disruptive microfluidic platform for engineering EV hybrids, offering a promising strategy to advance precision nanomedicine.

  PublisherOA PDFDOI

• Neoadjuvant-adjuvant pembrolizumab in clinical stage IIB/C melanoma.

  Journal of Clinical Oncology · 2025-05-28 · 7 citations

  article

  9502 Background: Neoadjuvant immune checkpoint therapy has shown improvement in event-free survival outcomes in patients with resectable clinical stage III and IV melanoma. Whether there is benefit to neoadjuvant immune therapy in patients with clinical stage IIB/C melanoma is unknown. Methods: In a single arm multicenter investigator-initiated phase 2 trial, patients with clinical stage IIB/C melanoma received a single dose of neoadjuvant pembrolizumab (200 mg intravenously) 3 weeks prior to wide excision and sentinel lymph node (SLN) biopsy followed by 1 year adjuvant pembrolizumab every 3 weeks or until unacceptable toxicity or disease progression. Primary endpoint was SLN positivity rate. A sample size of 63 patients had 80% power detect a 50% difference when compared to a predetermined historical SLN positivity rate in treatment naïve patients (25% Stage IIB and 40% Stage IIC) weighted by proportion of clinical tumor stage in eligible study patients. Secondary endpoint included recurrence-free survival. Safety outcomes, including overall toxicity and immune related adverse events, were also assessed. Results: Of 63 evaluable patients (33 IIB; 30 IIC at initial biopsy), the SLN metastasis rate in the neoadjuvant study group was 27%. 28 patients (44%) had residual primary tumor after single dose pembrolizumab; 4 patients had their primary tumors upstaged to IIC. Compared to a SLN metastasis rate in a historical treatment- naïve cohort based on tumor staging at wide excision (33.1%), there was a 18% reduction in SLN positivity rate in the neoadjuvant group, although this was not statistically significant (p = 0.302). In a subgroup analysis, stage IIC patients in the neoadjuvant study group had a SLN metastasis rate of 16.7% versus 40% (p = 0.009) based on initial biopsy and 23.5% versus 40% (p = 0.0499) based on primary tumor staging at wide excision. With median follow-up of 20.4 months, the 2-year recurrence free-survival in the study group was 84% with median time to recurrence (n = 10) of 9.9 months. Overall treatment-related grade 3/4 adverse events were 14 (22%) with 9 (14%) immune-related adverse events; there was no delay in definite surgery secondary to neoadjuvant treatment. Conclusions: Rate of SLN metastasis among patients with clinical stage IIB/C melanoma undergoing neoadjuvant pembrolizumab did not differ significantly compared to expected historical rates in treatment-naïve patients; however, in a secondary subgroup analysis among patients with clinical stage IIC disease, a decrease in SLN positivity rate was noted. Neoadjuvant therapy in clinical stage IIB/C was safe and feasible, with no significant delay in surgery or new or unexpected toxicities noted in these patients. Translational studies are under way, including flow cytometric and transcriptional studies, that may reveal immunologic determinants of efficacy versus resistance. Clinical trial information: NCT03757689 .

  PublisherDOI

• Preliminary evaluation of the safety and feasibility of toll-like receptor ligand CB101 combined with hypofractionated radiation therapy in canine head and neck cancer: a pilot study

  Veterinary oncology. · 2025-08-03 · 1 citations

  articleOpen access

  Radiation therapy (RT) is a common treatment modality for dogs with locally advanced head and neck tumors. Most dogs experience a clinical benefit secondary to RT, however, long term remissions are rare. This study evaluates the feasibility and safety profile of intratumoral CBC101 (a proprietary hydrogel-based injectable resiquimod formulation), a toll-like receptor (TLR) 7/8 agonist with immunomodulatory properties, when used in combination with radiation therapy. Three dogs with histologically confirmed head/neck cancers were prospectively enrolled. A baseline CT scan was performed. Dogs received palliative radiation therapy (8 Gy × 4) in conjunction with intratumoral CB101. A follow-up CT scan was performed at week 12 to assess tumor response and to evaluate for metastatic disease. Intratumoral CB101 was well-tolerated, feasible, and produced minimal adverse effects. Only one grade 1 adverse event was attributable to CB101; all other adverse events were expected radiation therapy side effects. The data obtained from this preliminary study will be used for further investigation into appropriate dosing and timing of intratumoral resiquimod or other TLRs, with eventual escalation into phase II and III clinical trials.

  PublisherOA PDFDOI

• Spatial profiling of chromatin accessibility in formalin-fixed paraffin-embedded tissues

  Nature Communications · 2025-07-01 · 11 citations

  articleOpen access

  Formalin-fixed paraffin-embedded (FFPE) samples represent a vast, untapped resource for epigenomic research, yet molecular tools for deep analysis of these specimens remain limited. We introduce spatial FFPE-ATAC-seq, an approach for in situ profiling chromatin accessibility within archived tissues. This approach overcomes formalin-induced crosslinking challenges, allowing high-resolution mapping of chromatin landscapes while preserving tissue architecture. Applying spatial FFPE-ATAC-seq to mouse and human tissues, including brain and thymus, reveals intricate spatial organization and distinct cell types in alignment with tissue morphology. Integration with single-cell RNA sequencing validates the precision of our chromatin profiles in identifying key cell types and regulatory elements. We further apply this method to human melanoma, comprehensively characterizing chromatin accessibility across both tumor and non-tumor regions. This method significantly expands the toolkit for epigenomic research, unlocking the potential of an extensive collection of archived FFPE samples for studying gene regulation and disease mechanisms with spatial context. FFPE tissues are widely used to preserve clinical specimens, but formalin-induced crosslinking limits their use in epigenomic profiling. Here, the authors present spatial FFPE-ATACseq, enabling in situ chromatin accessibility mapping while preserving tissue architecture in archived samples.

  PublisherOA PDFDOI

• Single-Dose Neoadjuvant Pembrolizumab in Resectable Metastatic Melanoma

  Annals of Surgical Oncology · 2025-09-12 · 2 citations

  articleOpen access

  INTRODUCTION: Neoadjuvant immune checkpoint blockade therapy for resectable oligometastatic melanoma has shown promising results in clinical trials; however, investigation into the optimal agent and dosing schedule is ongoing. We report on the largest case series of patients with oligometastatic melanoma treated with a single dose of neoadjuvant programmed cell death receptor 1 (PD-1) inhibition. METHODS: We identified PD-1 naive patients with resectable stage III/IV melanoma who received one dose of pembrolizumab (200 mg intravenous) prior to surgical resection at a single high-volume melanoma center. Outcomes included time to surgery, 30-day surgical complications, time to initiation of adjuvant therapy, major pathologic response (MPR) defined as < 10% viable tumor, patterns/treatment of first recurrence, and 5-year recurrence-free and overall survival. RESULTS: Of 51 patients, there were no grade 3/4 immune-related adverse events prior to surgery and no delays in surgery. The majority of patients (70.6%) had no postoperative complications, and none were Clavien-Dindo grade 3 or higher. There was prompt initiation of adjuvant therapy, along with appreciable rates of MPR (19.6%). In total, 45.1% of the cohort experienced a recurrence including two patients who had an MPR. For patients who achieved MPR, 5-year overall survival was 100%. CONCLUSIONS: A single dose of neoadjuvant pembrolizumab is a safe and feasible approach with potential for early pathological readout of responsiveness to neoadjuvant therapy. Late recurrences were observed in the MPR group, indicating need for follow-up but were salvageable. Further biomarker work is needed to identify patients who would benefit from neoadjuvant single agent anti-PD-1 therapy.

  PublisherOA PDFDOI

• Different retinal microvascular response to flicker light between normal-tension glaucoma and high-tension primary open-angle glaucoma detected with optical coherence tomography angiography

  Graefe s Archive for Clinical and Experimental Ophthalmology · 2025-10-22

  article
  PublisherDOI

• Effects of bundle-based preventive care on healthcare-associated infection control in neurosurgical patients

  Neurological Research · 2025-07-22

  article1st author

  OBJECTIVE: This study aims to investigate the effects of bundle-based preventive care on the control of healthcare-associated infections (HAIs) in patients undergoing neurosurgical procedures. METHODS: = 60), which bundle-based preventive care. The incidence of HAIs, antibiotic usage, and pathogen detection rates were compared between the two groups. In addition, adverse events and length of hospital stay were recorded. Nursing quality and patient satisfaction were also evaluated. RESULTS: < 0.05). CONCLUSION: Bundle-based preventive care can effectively reduce postoperative HAIs and antibiotic usage in neurosurgical patients, lower the incidence of adverse events, and significantly improve nursing quality and patient satisfaction.

  PublisherDOI

• Parous female donor is not inferior to the young male donor under the low-dose ATG/PTCy combination-based regimen for GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation

  Leukemia Research · 2025-05-26 · 3 citations

  article
  PublisherDOI

Recent grants

• Targeting HSP70 for MelanomaTherapy

  NIH · $69.3M · 2008–2025

• Developmental Research Program

  NIH · $17.8M · 2021

• NIH Grant R01AR054593

  NIH · $1.9M · 2015

• NIH Grant R21CA116103

  NIH · $389k · 2010

• Developmental Research Program

  NIH · $4.4M · 2019

Frequent coauthors

• Jing Wang

  765 shared

• Jing Wang

  255 shared

• Meenhard Herlyn

  207 shared

• Géza Ács

  171 shared

• T Pasha

  Hospital of the University of Pennsylvania

  155 shared

• Lynn M. Schuchter

  University of Pennsylvania

  131 shared

• Ravi K. Amaravadi

  120 shared

• Giorgos C. Karakousis

  93 shared