Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma

Abstract Background Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods The densities of TI...

Full description

Saved in:
Bibliographic Details
Main Authors: Sachie Kiryu, Zensho Ito, Machi Suka, Tsuuse Bito, Shin Kan, Kan Uchiyama, Masayuki Saruta, Taigo Hata, Yuki Takano, Shuichi Fujioka, Takeyuki Misawa, Takashi Yamauchi, Hiroyuki Yanagisawa, Nobuhiro Sato, Toshifumi Ohkusa, Haruo Sugiyama, Shigeo Koido
Format: article
Language:EN
Published: BMC 2021
Subjects:
TIL
Online Access:https://doaj.org/article/8336055c81c24d62a8789f312e8859d7
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. Results PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. Conclusion Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection.