Immune recurrence score using 7 immunoregulatory protein expressions can predict recurrence in stage I–III breast cancer patients

• Published in: British journal of cancer 2019-07, Vol.121 (3), p.230-236
• Main Authors: Lee, Dae-Won, Ryu, Han Suk, Jin, Min-Sun, Lee, Kyung-Hun, Suh, Koung Jin, Youk, Jeonghwan, Kim, Jung Youn, Min, Ahrum, Lee, Han-Byoel, Moon, Hyeong-Gon, Kim, Tae-Yong, Han, Sae-Won, Oh, Do-Youn, Han, Wonshik, Park, In Ae, Noh, Dong-Young, Im, Seock-Ah
• Format: Article
• Language: English
• Subjects: 631/250; 631/67/1347; Adult; Aged; B7 antigen; B7-H1 Antigen - analysis; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer Research; Disease-Free Survival; Drug Resistance; Epidemiology; ErbB-2 protein; Female; Humans; Immunoregulation; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Middle Aged; Molecular Medicine; Multivariate analysis; Neoplasm Recurrence, Local - etiology; Neoplasm Staging; Oncology; Ox40L protein; PD-1 protein; PD-L1 protein; Prognosis; Programmed Cell Death 1 Ligand 2 Protein - analysis; Protein expression; Proteins; Tumor microenvironment; Tumor necrosis factor; Tumorigenesis; Tumors
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-019-0511-9

Background Immune 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. Methods Expression 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. Results A 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. Conclusions This 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.