Abstract
BackgroundImmune cells in the tumour microenvironment play an essential role in tumorigenesis. This study aimed to evaluate the immunoregulatory protein expression of breast cancer and reveal their prognostic role.MethodsExpression of 10 immune markers (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/ B7-H3/B7-H4) with known/possible clinical relevance was identified in stromal tumour-infiltrating lymphocytes or tumour tissue of stage I–III breast cancer patients.ResultsA total of 392 patients, including 271(69.1%) luminal A, 36(9.2%) luminal B, 32(8.2%) HER2-positive and 53(13.5%) triple negative disease, were included. Expression of PD-1 and PD-L1 was higher in HER2-positive and triple negative disease. By contrast, expression of TIM-3, OX40 and OX40L were higher in luminal disease. We devised an immune recurrence score (IRS) using seven markers with prognostic value (B7-H2/B7-H3/B7-H4/OX40/OX40L/PD-L1/PD-L2). Patients were classified as high-risk (7.9%), intermediate-risk (67.6%), or low-risk (24.5%). In the multivariate analysis, IRS low-risk (adjusted HR 0.14, p = 0.001) and intermediate-risk (adjusted HR 0.32, p = 0.002) had significantly lower risk of recurrence compared with high-risk. The prognostic role of IRS was maintained in both luminal A and non-luminal A patients.ConclusionsThis study identified immunoregulatory protein expression of breast cancer patients using 10 immune markers. In addition, we devised an IRS which may predict recurrence in stage I-III breast cancer patients.
Highlights
Immune cells in the tumour microenvironment play an essential role in tumorigenesis
Atezolizumab plus nab-paclitaxel resulted in statistically significant PFS benefit for metastatic triple negative breast cancer patients as first line therapy.[6,7,8]
The PFS benefit in intention-to-treat patients were not translated into the overall survival benefit, the addition of atezolizumab showed clinically meaningful overall survival improvement in the programmed death ligand 1 (PD-L1) positive population
Summary
This study aimed to evaluate the immunoregulatory protein expression of breast cancer and reveal their prognostic role. We devised an immune recurrence score (IRS) using seven markers with prognostic value (B7-H2/B7-H3/B7-H4/OX40/OX40L/PD-L1/PD-L2). CONCLUSIONS: This study identified immunoregulatory protein expression of breast cancer patients using 10 immune markers. Besides the classical six hallmarks of cancer proposed by Hanahan et al, avoiding immune destruction has emerged as a new hallmark of cancer.[1] Complex interactions between cancer and immune system exist, which are controlled by multiple mechanisms Among these mechanisms, cancer cells can avoid immune destruction by alternating the immune checkpoint pathway. The overall response rate (ORR) of pembrolizumab was 18.5% of the 27 advanced triple negative breast cancer patients with at least 1% PD-L1 expression.[6] In a phase 1b
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