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Low intratumoral regulatory T cells and high peritumoral CD8+ T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy

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Abstract

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Recent studies have focused on the role of lymphocytes in the PDAC microenvironment. Using immunohistochemistry, our study explored the clinical significance of intratumoral or peritumoral CD4+Foxp3+ regulatory T cells (Tregs) and CD8+ T cells in the tumor microenvironment and analyzed their relation to the prognosis of PDAC in a consecutive series of 92 patients after resection. CD8+ T cells were more frequently seen within peritumoral sites, while CD4+Foxp3+ Tregs were more frequent within intratumoral areas. Neither exhibited any relationship with other clinicopathologic factors. Patients with low levels of intratumoral Tregs had longer disease-free survival than those with higher levels (DFS 22.2 vs. 11.2 months, p < 0.001), and patients with higher levels of peritumoral CD8+ T cells had longer overall survival than those with lower levels (OS 31.0 vs. 14.2 months, p < 0.001). Multivariate analysis demonstrated that intratumoral Tregs (hazard ratio, HR 3.39, p = 0.010) and peritumoral CD8+ T cells (HR 0.10, p < 0.001) are related to DFS and OS, respectively. These results indicate that intratumoral Tregs are a negative predictor of DFS, while peritumoral CD8+ T cells are a positive predictor of OS for PDAC patients with pancreatectomy.

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Abbreviations

CT:

Computed tomography

CTLs:

Cytotoxic T cells

DFS:

Disease-free survival

DP:

Distal pancreatectomy

FasL:

Fas ligand

GrB:

Granzyme B

HPF:

High-power fields

HR:

Hazard ratio

IHC:

Immunohistochemistry

MRI:

Magnetic resonance imaging

OS:

Overall survival

PD:

Pancreaticoduodenectomy

PDAC:

Pancreatic ductal adenocarcinoma

PPPD:

Pylorus-preserving pancreaticoduodenectomy

Th1:

T helper type 1

Th2:

T helper type 2

TILs:

Tumor-infiltrating lymphocytes

Tregs:

Regulatory T cells

UICC:

Union for International Cancer Control

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Acknowledgments

This work was supported by the following grants: the National Natural Science Foundation of China (Nos. 30801104, 81272731), the Science and Technology Commission of Shanghai Municipality (No. 11JC1402502), and the Public Welfare Industry of Health (No. 201202007).

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    Authors and Affiliations

    1. Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China

      Li Liu, Guochao Zhao, Wenchuan Wu, Yefei Rong, Dayong Jin, Dansong Wang & Xinyu Qin

    2. Institute of General Surgery, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China

      Wenhui Lou

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    Li Liu and Guochao Zhao have contributed equally to this work.

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    Liu, L., Zhao, G., Wu, W. et al. Low intratumoral regulatory T cells and high peritumoral CD8+ T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy. Cancer Immunol Immunother 65, 73–82 (2016). https://doi.org/10.1007/s00262-015-1775-4

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