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
  • 1Breast Disease Division, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, 14048-900 - Ribeirão Preto/BR
  • 2Breast And Gynecologic Oncology Division, HCRP-USP Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, 14048-900 - Ribeirão Preto/BR

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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.