171P - Tumour-immune system interactions in breast cancer: the role of PD-L1, PD-L2 and CD86 expression
Date | 28 September 2014 |
Event | ESMO 2014 |
Session | Poster Display session |
Topics | Breast Cancer Cancer Immunology and Immunotherapy Translational Research |
Presenter | Franklin Pimentel |
Citation | Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326 |
Authors |
F.F. Pimentel1, E.R. Chagas2, M.G. Tiezzi2, J.M. De Andrade2, D.G. Tiezzi2
|
Abstract
Aim
Despite recent advances in comprehension of cancer-immune system interactions in some tumours (i.e. melanoma and NSCLC), the role of these interactions in breast cancer has not been defined yet.
In this study, we analyzed the expression of PDL-1, PD-L2 and CD86 proteins in breast cancer and correlated to clinical data.
Methods
Paraffin-embedded tissue microarray was constructed enrolling 136 breast cancer biopsies. PD-L1, PD-L2 and CD86 were stained by immunohistochemistry assay with monoclonal antibodies (EPR 1161(2)-Abcam, MIH18-Biolegend, EP1158Y-Abcam, respectively). The slides were analysed by optical microscopy and considered positive when there were more than 10% of tumor cells stained with moderate intensity. Clinical and pathologic records were reviewed. Fisher exact test was used to establish association with variables. Log-rank was used to analyse overall survival.
Results
Tumours showed expression of PD-L1: 24% (24/98); PD-L2: 32% (42/130), CD86: 40% (44/110).
Statistically significant associations
Marker | p | ||
---|---|---|---|
PD-L1 | T1/T2: 34% | T3/T4: 14% | .03 |
N0: 41% | N1-3: 16% | .01 | |
PD-L2 | PD-L1 positive: 63% | PD-L1 negative: 27% | .002 |
CD86 | Premenopausal: 64% | Postmenopausal: 34% | .01 |
ER positive: 34% | ER negative: 57% | .03 | |
PR positive: 29% | PR negative: 57% | .003 | |
PD-L1 positive: 71% | PD-L1 negative: 34% | .002 | |
PD-L2 positive: 58% | PD-L2 negative: 33% | .01 | |
T1/T2: 53% | T3/T4: 25% | .004 | |
CS I/II: 49% | CS III/IV: 28% | .003 |
In clinical stage II/ CD86 positive group (n = 27), PD-L1 expression was significantly associated with better outcome (93% vs. 62% 5-year survival; p = 0.04).
Conclusions
PD-L1 expression was associated with early stage breast cancer: T1/T2 and N0 tumours.
CD86 expression was associated with worse prognostic factors: premenopausal status and negative ER/PR, but at early stage: T1/T2 tumours and CS I/II. PD-L2 expression was associated with PD-L1. CD86 expression was associated with PD-L1 and PD-L2. In the clinical stage II group, CD86+ PD-L1+ had better outcome than CD86+ PD-L1-.
Once these proteins are related to T cell inhibition and tumoral scape from immune system, it seems that breast cancer development has two phases. Firstly, early progression would require immune system inhibition. After, in advanced stages, this inhibition could be less important and the tumour would progress despite immune attack.
Therefore, considering these associations, more studies are needed to evaluate the role of these pathways in different stages of breast cancer.
Disclosure
All authors have declared no conflicts of interest.