77P - CXCL13 and tertiary lymphoid structures formation in the anti-breast cancer immune response

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Cancer Immunology and Immunotherapy
Translational Research
Presenter Edoardo Migliori
Citation Annals of Oncology (2015) 26 (suppl_3): 25-26. 10.1093/annonc/mdv118
Authors E. Migliori, C. Gu-Trantien, S. Garaud, L. Buisseret, H. Duvillier, J. Lodewyckx, L. Van Schoonwinkel, A. Boisson, K. Willard-Gallo
  • Molecular Immunology Unit, Institut Jules Bordet - Université Libre de Bruxelles, 1000 - Brussels/BE

Abstract

Body

Background: Our previous work has shown tertiary lymphoid structures (TLS) are associated with a good prognosis in breast cancer (BC). We further found that the presence of CD4+ follicular helper T (Tfh) cells in TLS signals an organized anti-tumor immune response and positive clinical outcomes. The aim of this study is to investigate the role the B cell chemoattractant CXCL13 plays in the development and/or maintenance of germinal center (GC)-like structures in BC-associated TLS and identify TLS markers. CXCL13 is expressed in high levels by GC resident Tfh cells.

Methodology: 1. Ten color flow cytometry was used to quantify CXCL13 production in primary CD4+ T cells, isolated from human peripheral blood and tonsils, after stimulation and/or treatment with cytokines modulating its expression. 2. Retrospective analysis of FFPE samples (N = 78) was assessed for CD72 and other GC-B and/or Tfh marker gene expression by qRT-PCR.

Results: 1. Our data reveal that anti-CD3/CD28 stimulation induces CXCL13 production by CD4+ and CD8+ T cells. Treatment using IL-2-blockade or TGF-beta1 both boosted chemokine production in stimulated cells, while IL-2 acted as a negative regulator. We also detected a negative correlation between CXCL13 and FoxP3 (a marker of CD4+ Regulatory T cells) production in cells treated with IL-2-blockade. 2. qRT-PCR data found that CD72 had value for predicting survival in BC, with LRMP/Jaw1, PAX5 and POU2AF1 also showing predictive potential. We determined that CD72 expression is positively correlated with Tfh genes, CXCL13, PDCD1 (PD1) and TIGIT, suggesting a relationship between CD72 regulation and Tfh activity in the tumour microenvironment.

Conclusions: These data show that CD4+ T cells (or a Th subset) can both maintain and increase CXCL13 production in response to activation signals. Further investigation is required to determine the mechanism of chemokine induction and in particular identify the critical genes regulating its production. These efforts will provide important insight into understanding the role Tfh and CXCL13 play in TLS (and GC) development. Together with the identification of B cell marker genes they should help identify the critical immune components involved in BC TLS formation.

Disclosure: All authors have declared no conflicts of interest.