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

BMC Cancer. 2021 Nov 10;21(1):1197. 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.

Keywords: Foxp3; Immune-related cells; PD-1; Pancreatic cancer; Prognosis; Surgical resection; TIL.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Pancreas / immunology
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatectomy
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • Retrospective Studies
  • Tumor Microenvironment / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor