PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients

Cancer Immunol Immunother. 2014 Apr;63(4):395-406. doi: 10.1007/s00262-014-1519-x. Epub 2014 Feb 11.

Abstract

The programmed death-1 (PD-1) molecule is mainly expressed on functionally "exhausted" CD8(+) T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8(+) cytotoxic T lymphocytes, FOXP3(+) (Treg cell marker), and PD-1(+) immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1(+) immune cells and FOXP3(+) Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1(+) cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1(+) immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation, T-Lymphocyte / analysis*
  • Apoptosis / immunology
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Ductal, Breast / immunology*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / radiotherapy
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Lobular / immunology
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / radiotherapy
  • Carcinoma, Lobular / surgery
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / analysis
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / chemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mastectomy
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / analysis*
  • Radiotherapy, Adjuvant
  • Survival Analysis
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Cytotoxic / chemistry
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor