Neoadjuvant FOLFIRINOX therapy is associated with increased effector T cells and reduced suppressor cells in patients with pancreatic cancer
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Abstract
Purpose: FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system. Experimental Design: Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF). Results: Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells. Conclusions: Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.
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Gammaproteobacteria in PDAC directly detoxify gemcitabine through expression of cytidine deaminase.
“gammaproteobacterial PDAC have been shown to directly detoxify gemcitabine through expression of cytidine deaminase267.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [267]
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Self-citation
- Authors
- Peng, H., James, C. A., Cullinan, D. R., Hogg, G. D., Mudd, J. L., Zuo, C., Takchi, R., Caldwell, K. E., Liu, J., DeNardo, D. G., Fields, R. C., Gillanders, W. E., Goedegebuure, S. P., & Hawkins, W. G.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Hawkins, William G.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2021-12-15
- Volume
- 27
- Issue
- 24
- Pages
- 6761-6771
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC8678309
- OpenAlex
- W3202028317
- Cited by
- 61
- References
- 50
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 19 · 2023: 16 · 2022: 16 · 2021: 1
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- NCI (T32 CA009621)
- The Washington University SPORE in Pancreas Cancer (P50CA196510)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- FOLFIRINOX, pancreatic ductal adenocarcinoma, neoadjuvant chemotherapy, tumor-infiltrating immune cells, regulatory T cells, effector T cells, CD39, inflammatory monocytes, Th1/Th2 balance, CD8+ T cells, CD4+ T cells, mass cytometry
- MeSH terms
- Irinotecan, Oxaliplatin, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Fluorouracil, Humans, Leukocytes, Mononuclear, Pancreatic Neoplasms, CD8-Positive T-Lymphocytes, Neoadjuvant Therapy
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