Ivan P. Maillard
· MD, PhDVerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1995–2026
About
Ivan P. Maillard, MD, PhD, is an Adjunct Professor of Medicine (Hematology-Oncology) at the University of Pennsylvania's Perelman School of Medicine. His laboratory investigates the regulation of normal and malignant hematopoiesis, bone marrow transplantation, and T cell alloimmunity. A central focus of his research is the role of Notch signaling in T cell development, differentiation, and function. Using mouse models of bone marrow transplantation, he has discovered essential functions for Notch receptors and ligands in graft-versus-host disease, with significant fundamental and translational impact. Additionally, his work explores the role of fibroblastic reticular cells as sources of Notch ligands and other signals in secondary lymphoid organs, emphasizing their emerging roles in immune regulation and in immunological and hematological disorders.
Research topics
- Medicine
- Biology
- Immunology
- Internal medicine
- Cancer research
- Genetics
- Cell biology
- Virology
Selected publications
Transplantation and Cellular Therapy · 2026-02-01
articleTransplantation and Cellular Therapy · 2026-02-01
articleUniversität Zürich, ZORA · 2026-02-02
articleOpen accessThe interaction of immune cells in the lymph node microenvironment depends on the infrastructure and molecular cues provided by fibroblastic reticular cells (FRCs). In addition, concentric layers of still poorly defined mural cells, including vascular smooth muscle cells (VSMCs), are involved in positioning and regulating immune cell interactions in different lymph node compartments. Using time-resolved single-cell transcriptomics, combined with cell fate mapping and high-resolution confocal microscopy, we found that lymph node FRCs and VSMCs share a proliferating, CCL19-expressing embryonic progenitor. Trajectory analysis identified lymphotoxin β receptor (LTβR)-dependent lineages that gave rise to FRCs underpinning the subcapsular sinus, T and B cell zones, and the medulla. LTβR-independent development of VSMCs and perivascular reticular cells from the common progenitor highlighted the close developmental relationship between FRCs and mural cells. Collectively, these results indicate that CCL19-expressing perivascular progenitors are capable of generating the fibroblastic and mural cell infrastructure of murine lymph nodes.
2025-09-04
preprintOpen access<p>OVA+ tumor growth in the LN does not depend on direct induction of tumor-specific Tregs by tumor MHC-II</p>
2025-09-04
preprintOpen access<p>Metastatic patterns of colon cancer differ by MSI status</p>
2025-09-04
articleOpen access<p>Tumor reactive OT-I T cells are more cytotoxic in blood than in tumor draining lymph nodes</p>
Blood · 2025-11-03
articleOpen accessAbstract Introduction: Second-line (2L) anti-CD19 CAR T-cell therapy (CART) with axicabtagene ciloleucel (axi) or lisocabtagene maraleucel (liso) is standard-of-care for patients (pts) with large B-cell lymphomas (LBCLs) who relapse within 12 months after frontline treatment. However, determinants of response and toxicity in 2L real-world settings remain poorly defined. Methods: We retrospectively analyzed 64 consecutive LBCLs pts treated at our institution with 2L axi (n=35) or liso (n=29) between 05/2022 and 12/2024. Multiparameter spectral immunophenotyping (Citek) was performed on peripheral blood collected at apheresis and day 7 post-CART. The primary objectives were to compare the two products in a real-world setting and to identify predictors of efficacy and toxicity. Results: Median age at time of CART was 62 years (21-80yrs); 59% had primary refractory LBCL, 17% had an HGBL, 66% had III/IV-stage and 38% had elevated LDH at infusion. Median vein-to-vein time was 42 days (median axi=36 vs liso=43; p=0.03). Bendamustine was used for lymphodepletion in 89% (axi=83% vs liso=96%, p=0.1). Overall and complete response rates (ORR and CR) at day 90 were 66% and 55%.At a median follow-up of 17 months (4-34mo), 12-month PFS and OS rates were 47% and 78%. Efficacy was comparable between axi and liso (12-month PFS: 51% vs 48%, p=0.8; best CR: 51% vs 58%, p=0.6), despite older age (mean 56 vs 66yrs, p&lt;0.01) and higher IPI (≥3 in 28% vs 72%, p&lt;0.01) in the liso cohort.Cytokine release syndrome (CRS) of any grade occurred in 52% of pts (G≥3 = 3%) and neurotoxicity (ICANS) in 12% (G≥3 = 3%). No non-relapse mortality or secondary malignancies occurred. Axi was associated with higher toxicity, with increased rates of CRS (any grade: 80% vs 17%, p&lt;0.01) and a trend towards higher ICANS (any grade: 20% vs 3%, p=0.06). Due to few severe CRS/ICANS events, comparisons between axi and liso were not performed.Disease reassessment after bridging therapy was available for 92% of pts and 34% were infused in progression. Pts infused with progressive disease had worse outcomes as compared to those with disease control: CR as best response in 15% vs 73% (OR=0.06 95%CI=0.01-0.3, p&lt;0.01), 12-month OS 48% vs 91% (p&lt;0.01), and PFS 21% vs 59% (p&lt;0.01). Bulky disease, extranodal involvement, and elevated LDH at infusion were negative predictors of durable response (defined as PFS≥12 months); interestingly these features were not prognostic when analyzed at the relapse after the frontline therapy.Given the prognostic value of clinical variables at infusion but not at relapse, we explored flow cytometry to identify early predictors of treatment response. Higher CD3⁺ and CD4⁺ T-cell counts at apheresis predicted PFS and CR to CART. Optimal cutoffs (401 CD3⁺/µL, 201 CD4⁺/µL) stratified pts with significantly prolonged 12-month PFS rates (59% vs 29% for CD4⁺; p&lt;0.01). High Naive CD4⁺ T-cell at apheresis strongly correlated with durable responses and prolonged PFS (12-month PFS rates: 12% vs 87%, p&lt;0.01).At day 7, responders showed a trend toward greater CART expansion (CAR⁺/CD3⁺: 17% vs 6%, p=0.1) and higher frequencies of naive CD8⁺CART. In contrast, pts infused with progressive disease had numerically lower CART expansion and a more differentiated effector memory phenotype (CAR+/CD3+: 5% vs 14%, p=0.1 and CD45RA-/CCR7-: 54% vs 38%, p=0.3). CAR⁻ bystander T-cells showed a more naive CD4⁺ and less effector CD8⁺ profile indicating functional divergence from CART.In multivariate analysis including CD4⁺ count at apheresis, disease progression at infusion, and primary refractory status, higher CD4⁺ count remained independently associated with higher odds of CR (OR=4.31, 95%CI=1.15-18.8, p=0.03). Progressive disease at infusion (OR=0.06, 95%CI=0.01-0.3, p&lt;0.01) and primary refractory disease(OR=0.2, 95%CI=0.05-0.8, p=0.03) were associated with lower odds of CR. Conclusions: This is the first real-world study to define clinical and immune correlates of efficacy in 2L CART therapy for LBCL. Both axi and liso are safe and effective. Naïve CD4⁺ T-cell abundance at apheresis predicts long-term outcomes and may serve as a biomarker of T-cell fitness and CART potency. Progressive disease at the time of infusion is associated with inferior response rates and survival outcomes, which may be due to less favorable expansion kinetics and T-cell phenotypes. These findings support immune profiling at apheresis and rational bridging to improve outcomes in early-line CART therapy.
2025-09-04
preprintOpen access<p>Regulatory T cells control tumor-specific CD8 cytotoxicity by IL-2 restriction</p>
2025-09-04
preprintOpen access<p>Tregs confer protective advantage to OVA+ tumor cells after intra-LN injection</p>
Notch2 signaling instructs viral and bacterial TLR responsiveness in B cells
bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-12
preprintOpen accessMarginal zone (MZ) B cells are hyperresponsive to bacterial Toll-like Receptor (TLR) ligands. However, the full extent of TLR responsiveness for MZ B cells and the mechanisms regulating such responses are unclear. We report that Notch2 activation establishes MZ B cell responsiveness for the viral dsRNA receptor TLR3 and augments responses for the LPS receptor TLR4. Notch2 ligation accelerated Myc induction, mitosis, and plasma cell differentiation to LPS. Further, TLR3 expression in MZ B cells was Notch2 dependent, and ectopic Notch2 signaling was sufficient to promote robust TLR3 responsiveness dependent on the TIR-domain-containing adapter TRIF and the kinase BTK. TLR3 engagement in MZ B cells promoted proliferation, differentiation, and the secretion of IgG2b and IgG2c antibodies. Our results establish a novel role for Notch2 in establishing TLR3 and TLR4 responsiveness in B cells and suggest that MZ B cells play unappreciated roles in immunity against RNA viruses.
Recent grants
Notch Signaling in Alloimmunity
NIH · $6.4M · 2011–2027
Hematology Clinical Research Training Program
NIH · $16.4M · 1979–2029
Molecular functions of the shelterin component ACD/TPP1 in somatic stem cells and tissue homeostasis
NIH · $2.3M · 2015–2021
Frequent coauthors
- 177 shared
Warren S. Pear
- 66 shared
Lanwei Xu
University of Pennsylvania
- 64 shared
Olga Shestova
University of Pennsylvania
- 60 shared
Jon C. Aster
Brigham and Women's Hospital
- 58 shared
Eric Perkey
University of Chicago
- 51 shared
Hong Sai
Lanzhou University
- 51 shared
Ann Friedman
University of Michigan–Ann Arbor
- 40 shared
Bruce R. Blazar
University of Minnesota
- Resume-aware match score
- Save to shortlist
- AI-drafted outreach
See your match with Ivan P. Maillard
PhdFit ranks faculty by your research interests, methods, and publications — grounded in their actual work, not templates.
- Free to start
- No credit card
- 30-second signup