79P - Expression of transcription factor FOXP1 in the immune response to breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Cancer Immunology and Immunotherapy
Translational Research
Presenter Pushpamali De Silva
Citation Annals of Oncology (2015) 26 (suppl_3): 25-26. 10.1093/annonc/mdv118
Authors P. De Silva1, S. Garaud1, E. Migliori1, C. Solinas1, A. Boisson1, C. Naveaux1, S. Pecenko1, R. de Wind2, D. Larsimont3, K. Willard-Gallo1
  • 1Molecular Immunology Unit, Institute Jules Bordet, 1000 - Brussels/BE
  • 2Anatomical Pathology Department, Institute Jules Bordet, 1000 - Brussels/BE
  • 3Anatomical Pathology Department, Institute Jules Bordet, Brussels/BE

Abstract

Body

High lymphocyte infiltration predicts improved disease outcome among breast cancer (BC) patients. Our previous work demonstrated that tumor infiltrating lymphocytes (TIL) in extensively infiltrated tumors are organized in distinct CD3+ T cell and CD20+ B cell zones in tertiary lymphoid structures (TLS) located adjacent to the tumor bed. However, the mechanisms involved in the establishment of these anti-tumor immune responses and the effectiveness of this immune infiltrates remain unclear. Recently, T cell unresponsiveness driven by FOXP1 upregulation, a not well studied member of the Foxp transcription factor subfamily, was shown to occur in tumor-associated CD8+ T cells. FOXP1 is a known tumor suppressor although it is differentially expressed in various tumor types; in BC FOXP1 expression predicts better patient outcome. The aim of this study was to understand the role of FOXP1 in generating effective anti-tumor immune responses in human BC. Analysis of global microarray data from an untreated patient population revealed that FOXP1 expression decreases from less aggressive Luminals to more aggressive HER2+ and Triple negative (TN) BC subtypes. Immunohistochemical analysis of Foxp1 in 24 prospectively collected FFPE BC tissue samples (62% luminal A, 17% luminal B, 12% triple-negative, 9% HER2) revealed considerable increase in nuclear Foxp1 positivity in the Luminals compared to TN and HER2+ subtypes. In this cohort, significant increase in Foxp1 expression was detected in lymphocytes located within TLS than tumor infiltrating lymphocytes located outside TLS (p = 0.0294). However, Foxp1 expression was not correlated to number of TLS present in the tumor bed or TIL infiltration. The pattern of Foxp1 expression is not as well organized in TLS as in secondary lymphoid structures suggesting that aberrant expression of FOXP1 could impair lymphocyte arrangement inside TLS, an aspect currently under further investigation. Our data suggest that expression of FOXP1 is associated with a better clinical outcome in BC and its increased expression in TLS may play an important functional role in generating anti-tumor immune responses.

Disclosure: All authors have declared no conflicts of interest.