ArticleJCI insight2022
Neoadjuvant chemotherapy drives intratumoral T cells toward a proinflammatory profile in pancreatic cancer.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- TIGITCancers · 2026Article
- Article
- Extracellular vesicles from chemotherapy-induced senescent tumor cells reprogram hepatic phospholipid metabolism to promote pancreatic cancer liver metastasis.Journal of experimental & clinical cancer research : CR · 2026Article
- Selective targeting of NRF2-high pancreatic ductal adenocarcinoma with an NQO1-activatable prodrug.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma.Frontiers in immunology · 2026Article
- Review
- Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.Molecular cancer therapeutics · 2024Article
- Updates in Immunotherapy for Pancreatic Cancer.Journal of clinical medicine · 2024Review
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2024Article
- The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer.Journal of cancer research and clinical oncology · 2023Article
- Serum immune checkpoint profiling identifies soluble CD40 as a biomarker for pancreatic cancer.NPJ precision oncology · 2023Article
- Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor.Journal of clinical medicine · 2023Review
- Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results.Cancers · 2023Review
- TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Reshaping the Pancreatic Cancer Microenvironment at Different Stages with Chemotherapy.Cancers · 2023Review
- Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. At diagnosis, only 20% of patients with PDAC are eligible for primary resection. Neoadjuvant chemotherapy can enable surgical resection in 30%-40% of patients with locally advanced and borderline resectable PDAC. The effects of neoadjuvant chemotherapy on the cytokine production of tumor-infiltrating T cells are unknown in PDAC.METHODSWe performed multiplex immunofluorescence to investigate T cell infiltration in 91 patients with PDAC. Using flow cytometry, we analyzed tumor and matched blood samples from 71 patients with PDAC and determined the frequencies of T cell subsets and their cytokine profiles. Both cohorts included patients who underwent primary resection and patients who received neoadjuvant chemotherapy followed by surgical resection.RESULTSIn human PDAC, T cells were particularly enriched within the tumor stroma. Neoadjuvant chemotherapy markedly enhanced T cell density within the ductal area of the tumor. Whereas infiltration of cytotoxic CD8+ T cells was unaffected by neoadjuvant chemotherapy, the frequency of conventional CD4+ T cells was increased, and the proportion of Tregs was reduced in the pancreatic tumor microenvironment after neoadjuvant treatment. Moreover, neoadjuvant chemotherapy increased the production of proinflammatory cytokines by tumor-infiltrating T cells, with enhanced TNF-α and IL-2 and reduced IL-4 and IL-10 expression.CONCLUSIONNeoadjuvant chemotherapy drives intratumoral T cells toward a proinflammatory profile. Combinational treatment strategies incorporating immunotherapy in neoadjuvant regimens may unleash more effective antitumor responses and improve prognosis of pancreatic cancer.FUNDINGThis work was supported by the Jung Foundation for Science and Research, the Monika Kutzner Foundation, the German Research Foundation (SE2980/5-1), the German Cancer Consortium, and the Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden.
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