TY - JOUR
T1 - Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer
AU - Peng, Hui
AU - James, C. Alston
AU - Cullinan, Darren R.
AU - Hogg, Graham D.
AU - Mudd, Jacqueline L.
AU - Zuo, Chong
AU - Takchi, Rony
AU - Caldwell, Katharine E.
AU - Liu, Jingxia
AU - DeNardo, David G.
AU - Fields, Ryan C.
AU - Gillanders, William E.
AU - Goedegebuure, S. Peter
AU - Hawkins, William G.
N1 - Funding Information:
D.R. Cullinan reports grants from NIH during the conduct of the study. J. Liu reports grants from NIH during the conduct of the study. W.E. Gillanders reports grants from NIH and Centene during the conduct of the study. W.G. Hawkins reports grants from NCI and Washington University-Centene ARCH Personalized Medicine Initiative during the conduct of the study as well as non-financial support from Celldex Corporation and other support from Accuronix Therapeutics outside the submitted work. No disclosures were reported by the other authors.
Funding Information:
This work was supported by NCI T32 CA009621 (C.A. James, K.E. Caldwell, D.R. Cullinan), The Washington University SPORE in Pancreas Cancer P50CA196510 (J.L. Mudd, G.D. Hogg, C. Zuo, J. Liu, D.G. DeNardo, R.C. Fields, W.E. Gillanders, S.P. Goedegebuure, W.G. Hawkins), and Centene Corporation contract P19-00559 (H. Peng, R. Takchi, S.P. Goedegebuure, D.G. DeNardo, R.C. Fields, W.E. Gillanders, W.G. Hawkins) for the Washington University-Centene ARCH Personalized Medicine Initiative.
Publisher Copyright:
© 2021 The Authors.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85120538832&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-0998
DO - 10.1158/1078-0432.CCR-21-0998
M3 - Article
C2 - 34593529
AN - SCOPUS:85120538832
SN - 1078-0432
VL - 27
SP - 6761
EP - 6771
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -