Abstract
Purpose
Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3, and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC).
Methods
A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry.
Results
There were 47 (26.6%) patients with high LAG-3 expression, 31 (17.5%) patients had high TIM-3 expression, and 32 (18.1%) patients had high OX-40 expression. The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p = 0.038) and HER2-enriched breast cancer (HER2BC) (p = 0.021), and the total number of pathological complete response (pCR) patients was greater (p < 0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p < 0.001) (p = 0.020). Moreover, on multivariate analysis also showed that low-LAG-3 expression status was an independent factor to predict the favorable prognosis (p = 0.014, HR = 8.124) (p = 0.048, HR = 10.400).
Conclusions
Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.
Changes of Tumor Infiltrating Lymphocytes after Core Needle Biopsy and the Prognostic Implications in Early Stage Breast Cancer: A Retrospective Study