ArticleCancer immunology research2024
Blockade of IL1β and PD1 with Combination Chemotherapy Reduces Systemic Myeloid Suppression in Metastatic Pancreatic Cancer with Heterogeneous Effects in the Tumor.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed.
- Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer.Journal for immunotherapy of cancer · 2026Trial
- Interleukin-1α (IL-1α) in pancreatic ductal adenocarcinoma: implications for immunotherapy and molecular biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- Article
- Review
- Dendritic cell redundancy enables priming of anti-tumor CD4Cancer cell · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Article
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Deciphering immunosuppressive niches by spatial single-cell proteomics: spatial interaction networks and translational opportunities.Frontiers in immunology · 2026Review
- Identification of immunosuppressive neutrophils using multi-omics: why functional testing remains key.Frontiers in immunology · 2026Review
- The Prospects of Palmitylethanolamide in Tumor Prevention and Treatment.Journal of inflammation research · 2026Review
- IL-20 Subfamily Biological Effects: Mechanistic Insights and Therapeutic Perspectives in Cancer.International journal of molecular sciences · 2025Review
- A phase 0, window of opportunity study of parasympathetic stimulation with bethanechol in localized pancreatic adenocarcinoma prior to surgery.The oncologist · 2025Article
- IL-1β blockade prevents cardiotoxicity and improves the efficacy of immune checkpoint blockers and chemotherapy against pancreatic cancer in mice with obesity.Journal for immunotherapy of cancer · 2025Article
- Real-World pharmacovigilance analysis of drug-related conjunctivitis using the FDA adverse event reporting system database.Scientific reports · 2025Article
- Distinct response to IL-1β blockade in liver- and lung-specific metastasis mouse models of pancreatic cancer with heterogeneous tumor microenvironments.Experimental hematology & oncology · 2025Article
- Cytokines in cancer.Cancer cell · 2025Review
- Multi-omics dissection of tumor microenvironment-mediated drug resistance: mechanisms and therapeutic reprogramming.Frontiers in pharmacology · 2025Review
- Mechanistic insights curcumin's anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interferenceFrontiers in cell and developmental biology · 2025Article
Corrections and comments
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Authors and funding
41 authors.
Funding
Abstract
Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1β blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n = 10) were treated with canakinumab, a high-affinity monoclonal human antiinterleukin-1β (IL1β), the PD1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSC) by flow cytometry for patients in the trial but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor, we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD1 and IL1β blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.
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Registered trials
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