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Articles by Drew Pardoll
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial
Abstract Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM.
γδ T cell-stromal networks modulate matrix composition and vascularity in foreign body response
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Abstract Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how γδ T cell interactions with stromal cells shape fibrosis in the foreign body response in a murine biomaterial implant model. During the acute reaction, type-1 (γδIFNγ) and type-17 (γδ17) γδ T cell subsets accumulate at the implant site.
By Anna Ruta, Kavita Krishnan, Jiwon Woo, Joscelyn C. Mejias, Elise Gray-Gaillard, David R. Jr., Helen Nguyen, Helen Nguyễn, Alexandra Rindone, Christopher Cherry, Michael Patatanian, Frank Yu, Brenda Yang, Connor D. Amelung, Christina King, Birgit Schilling, Sharon Gerecht, Elana Fertig, Locke Davenport Huyer, Drew Pardoll, Jennifer H. Elisseeff
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Nature
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Retraction Note: Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer
Retraction to: Nature Communications https://doi.org/10.1038/s41467-022-28509-z, published online 15 February 2022 The authors have retracted this article because there are duplicate cells in the Source Data for the following figure panels: Figure 1 panels d and e, Figure 2 panels a,b c and h, Figure 3 panels c and d, Figure 5 panel b, Figure 6 panels b and c, Figure 7 panels b, c and d, Figure S2 panels b, c and d, Figure S3 panel b, Figure S12, Figure S13 panels b, d and e, Figure S14...
TRBC2-targeting antibody–drug conjugates for the treatment of T cell cancers - Nature Cancer
Abstract Antibody–drug conjugates (ADCs) have been remarkably successful in treating solid and hematological malignancies. Generation of ADCs for T cell cancers is challenging because the ADCs must selectively target cancerous T cells while sparing some normal T cells necessary for immune function. T cells express one of two TRBC alleles: TRBC1 or TRBC2. Normal T cells are composed of about 40% TRBC1-expressing and 60% TRBC2-expressing cells.
Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses - Nature Medicine
Abstract Immune checkpoint blockade (ICB) is standard of care in advanced diffuse pleural mesothelioma (DPM), but its role in the perioperative management of DPM is unclear. In tandem, circulating tumor DNA (ctDNA) ultra-sensitive residual disease detection has shown promise in providing a molecular readout of ICB efficacy across resectable cancers.
Author Correction: First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial | Nature Medicine
Correction to: Nature Medicine https://doi.org/10.1038/s41591-024-03450-4, published online 22 January 2025. In the version of this article initially published, the labels “≥5” and “<5” were missing from the PD-L1 CPS at baseline (22C3) column in Fig. 1d; in Fig. 3a–c, the y-axis labels “PFS (%)” now replace overall survival “OS (%),” while in Fig. 3a, the hazard ratio value “0.53” now replaces the original “0.55.” The figures are updated in the HTML and PDF versions of the article.
A minimal gene set characterizes TIL specific for diverse tumor antigens across different cancer types - Nature Communications
Abstract Identifying tumor-specific T cell clones that mediate immunotherapy responses remains challenging. Mutation-associated neoantigen (MANA) -specific CD8+ tumor-infiltrating lymphocytes (TIL) have been shown to express high levels of CXCL13 and CD39 (ENTPD1), and low IL-7 receptor (IL7R) levels in many cancer types, but their collective relevance to T cell functionality has not been established.
First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial | Nature Medicine
Abstract Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression.
Neoadjuvant anti-PD-1-based immunotherapy: evolving a new standard of care
Neoadjuvant anti-PD-1-based immunotherapy: evolving a new standard of care Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
TRBC1-targeting antibody–drug conjugates for the treatment of T cell cancers - Nature
Abstract Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic malignancies1,2,3,4,5,6,7,8,9. Adults with T cell leukaemias and lymphomas, collectively called T cell cancers, have short survival10,11 and lack such targeted therapies. Thus, T cell cancers particularly warrant the development of CAR T cells and antibodies to improve patient outcomes.
Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses | Nature Medicine
Abstract Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors.
Radiation Therapy and Myeloid-Derived Suppressor Cells: Breaking Down Their Cancerous Partnership
Radiation therapy (RT) has been a primary treatment modality in cancer for decades. Increasing evidence suggests that RT can induce an immunosuppressive shift via upregulation of cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). MDSCs inhibit antitumor immunity through potent immunosuppressive mechanisms and have the potential to be crucial tools for cancer prognosis and treatment.
Author Correction: DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires
Correction to: Nature Communications https://doi.org/10.1038/s41467-021-21879-w, published online 11 March 2021.
DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires
Abstract Deep learning algorithms have been utilized to achieve enhanced performance in pattern-recognition tasks. The ability to learn complex patterns in data has tremendous implications in immunogenomics. T-cell receptor (TCR) sequencing assesses the diversity of the adaptive immune system and allows for modeling its sequence determinants of antigenicity.
Neoadjuvant checkpoint blockade for cancer immunotherapy
Presurgical immune checkpoint blockade Checkpoint blockade immunotherapy using antibodies that inhibit the programmed cell death 1 (PD-1) or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) pathways has resulted in unprecedented clinical outcomes for certain cancers such as melanoma. Topalian et al. review advances in neoadjuvant (presurgical) immunotherapy as an important next step for enhancing the response of early-stage tumors to immune checkpoint blockade.
Neoadjuvant nivolumab induces pathologic responses in advanced resectable non-small cell lung cancer
Disclosure: Pardoll reports consultant roles with Aduro Biotech, Amgen, Bristol-Myers Squibb, DNAtrix, DNAX, Dracen, Five Prime Therapeutics, FixBio, Immunomic, Janssen, MedImmune, Merck, Pfizer, Potenza, Tieza, Tizona and WindMIL; stock ownership in Aduro Biotech, DNAtrix, Dracen, Five Prime Therapeutics, FixBio, Tieza, Tizona and WindMIL; and patents with Aduro Biotech, Bristol-Myers Squibb, Immunomic and WindMIL.
The intestinal microbiome influences checkpoint blockade
AffiliationsCynthia L. Sears and Drew M.
How immunotherapy helps cancer patient’s own body attack tumors
“I like to think of [immunotherapy] like a car. To get from Point A to B with a car, you need three things: You need the gas pedal to go, but you also need the brakes, and it also helps to have a steering wheel. The immune system can steer itself very carefully and in a very focused way. In fact, it’s the genetic signatures in a cancer cell that the immune system can use to distinguish a cancer cell from a normal cell. .?.?.
Caspase-1 from MDSC promote MyD88 dependent carcinogenesis that is T-cell independent
Myeloid-derived-suppression cells (MDSC) are functionally defined to suppress T-cells in their primary means of immune evasion mechanism in cancer. However, we have discovered that MDSC can have direct, T-cell independent pro-carcinogenic effect on tumor cells. Sorted monocytic CD14+/CD11b+/HLA-DRlowMDSCs from head and neck squamous cell carcinoma (HNSCC) patients were found to increase the proliferation index of HNSCC cells.
Micromanging lupus nephritis: miR17-92 modulates regulatory T cell activity by targeting foxp3 co-regulators
Regulatory T (Treg) cells play a critical role in maintaining self-tolerance and controlling the magnitude of physiologic immune response. The Treg transcription factor forkhead box P3 (Foxp3) works in concert with other co-regulator molecules including Eos to determine suppressive phenotype of Treg. A strong correlation between systemic lupus erythematous and deficiencies of Treg has been reported. We induce pristane nephropathy on T cell specific miR-17-92 knockout mice.
The Neurotrophic Factor Neuritin Maintains and Promotes the Function of Regulatory T cells in Autoimmunity and Cancer
Regulatory T cells (Tregs) enforce immune homeostasis and self-tolerance and inhibit both natural and induced anti-tumor immunity. Consequently, there is considerable interest in therapeutic Treg enhancement or blockade to treat inflammatory/autoimmune diseases and cancer, respectively. Targeting Tregs requires a comprehensive understanding of the factors important for their maintenance, differentiation and function.
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