Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
By: Kiryu, Sachie, Ito, Zensho, Suka, Machi, Bito, Tsuuse, Kan, Shin, Uchiyama, Kan, Saruta, Masayuki, Hata, Taigo, Takano, Yuki, Fujioka, Shuichi, Misawa, Takeyuki, Yamauchi, Takashi, Yanagisawa, Hiroyuki, Sato, Nobuhiro, Ohkusa, Toshifumi, Sugiyama, Haruo, Koido, Shigeo

BioMed Central
2021-11-10; doi: 10.1186/s12885-021-08911-4

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.







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