ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Neoadjuvant Chemotherapy Is Associated with Altered Immune Cell Infiltration and an Anti-Tumorigenic Microenvironment in Resected Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The trial behind it
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Who cites it
56 citing papers in PubMed, 70 citations in OpenAlex.
- Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.Nature cancer · 2026Trial
- Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.Cancer discovery · 2024Trial
- Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial.Nature communications · 2024Trial
- Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma.Journal for immunotherapy of cancer · 2023Trial
- Polarization of tumor-infiltrating macrophages predicts complete response to neoadjuvant treatment in patients with rectal cancer.Oncoimmunology · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Computed tomography quantitative imaging features for pancreatic ductal adenocarcinoma after neoadjuvant therapy: a narrative review.Gland surgery · 2026Review
- Dendritic cell redundancy enables priming of anti-tumor CD4Cancer cell · 2026Article
- Impact of vitamin D on the colon cancer immune microenvironment: results of a randomized clinical trial of preoperative vitamin D supplementation in patients with stage I-III colon cancer.Cancer discovery · 2026Article
- Review
- Survival after resection of pancreatic cancer is similar with neoadjuvant gemcitabine-nab-paclitaxel or mFOLFIRINOX but one size will not fit all in the future.Hepatobiliary surgery and nutrition · 2026Article
- 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
- Agonistic GITR treatment enhances antitumor immune responses and suppresses tumor progression in pancreatic ductal adenocarcinoma.Journal of gastroenterology · 2026Article
- Review
- Extracellular vesicle-derived miRNA-182-5p educates macrophages towards an immunosuppressive phenotype in pancreatic cancer.Signal transduction and targeted therapy · 2026Article
- T-cell Subset Features and Distributions Evolve across the Colorectal Precancer-Cancer Spectrum.Cancer immunology research · 2026Article
- Impact of biliary fungal contamination on outcomes after pancreaticoduodenectomy for pancreatic cancer.Frontiers in oncology · 2026Article
- Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma.Frontiers in immunology · 2026Article
- Biomimetic Cell Membrane-coated Nanovaccines in Anti-tumor Immunotherapy.Theranostics · 2026Review
- Nonredundant Immune Checkpoints Direct Therapeutic Resistance to Chemoimmunotherapy in Pancreatic Ductal Adenocarcinoma.Cancer immunology research · 2025Article
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 2 countries.
Funding
Abstract
purposeNeoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood. EXPERIMENTAL:
designWe employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient outcomes.
resultsIn the multi-institutional resection cohort, immune cells exhibited substantial heterogeneity across patient tumors and were located predominantly in stromal regions. Unsupervised clustering using immune cell densities identified four main patterns of immune cell infiltration. One pattern, seen in 20% of tumors and characterized by abundant T cells (T cell-rich) and a paucity of immunosuppressive granulocytes and macrophages, was associated with improved patient survival. Neoadjuvant chemotherapy was associated with a higher CD8:CD4 ratio, greater M1:M2-polarized macrophage ratio, and reduced CD15+ARG1+ immunosuppressive granulocyte density. Within neoadjuvant-treated tumors, 72% showed a T cell-rich pattern with low immunosuppressive granulocytes and macrophages. M1-polarized macrophages were located closer to tumor cells after neoadjuvant chemotherapy, and colocalization of M1-polarized macrophages and tumor cells was associated with greater tumor pathologic response and improved patient survival.
conclusionsNeoadjuvant chemotherapy with FOLFIRINOX shifts the PDAC immune microenvironment toward an anti-tumorigenic state associated with improved patient survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.