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Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Case report: Diverse immune responses in advanced pancreatic ductal adenocarcinoma treated with immune checkpoint
Xiaoying Li1, Chaoxin Xiao2, Ruizhen Li1
1Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, presenting limited therapeutic options and a grim prognosis due to its aggressive nature. Despite ongoing exploration of various combination therapies, a standardized treatment approach after the first-line treatment progress remains elusive. This report details the cases of two patients with unresectable advanced PDAC who underwent distinct conversion treatment regimens involving immune checkpoint inhibitors (ICIs). Remarkably, both patients became eligible for surgery following different anti-PD-1 antibody-based conversion therapies, ultimately achieving R0 resection. In essence, our findings highlight the efficacy of the anti-PD-1 antibody combined with a tyrosine kinase inhibitor (TKI) regimen and chemotherapy alongside anti-PD-1 antibody as viable conversion therapies for preoperative advanced PDAC. Tumor immune microenvironment (TIME) analysis underscores the intratumoral and intertumoral heterogeneity observed in the postoperative immune landscape of surgical specimens. This insight contributes to a deeper understanding of the potential benefits of these conversion therapies in addressing the challenging landscape of advanced PDAC.
Insights
Advanced pancreatic cancer (PDAC) treatment is challenging. Conversion therapies using anti-PD-1 antibodies with chemotherapy or TKIs enabled surgery in two patients, showing promising results for unresectable PDAC.
Area of Science:
- Oncology
- Immunotherapy
- Surgical Oncology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) frequently presents at advanced stages with limited treatment options.
- Standardized treatment for advanced PDAC post-first-line therapy remains an unmet clinical need.
- Immune checkpoint inhibitors (ICIs) are being explored for various advanced cancers.
Observation:
- Two patients with unresectable advanced PDAC received distinct conversion therapies involving anti-PD-1 antibodies.
- Both patients achieved surgical eligibility and R0 resection after these preoperative treatments.
- Tumor immune microenvironment (TIME) analysis revealed significant heterogeneity in postoperative specimens.
Findings:
- Anti-PD-1 antibody combined with a tyrosine kinase inhibitor (TKI) regimen demonstrated efficacy.
- Chemotherapy combined with anti-PD-1 antibody also proved effective as a conversion therapy.
- These regimens facilitated conversion to resectable disease in advanced PDAC.
Implications:
- These findings suggest that anti-PD-1 antibody-based conversion therapies are viable options for advanced PDAC.
- Understanding TIME heterogeneity is crucial for optimizing treatment strategies.
- This approach offers potential for improved outcomes in patients with initially unresectable PDAC.
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