Abstract
Background“Avoiding immune destruction” has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer.MethodsA total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry.ResultsThere were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479).ConclusionsPD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC.
Highlights
Various immunosuppressive factors from cancer cells in the tumor microenvironment inhibit host immune responses to cancer [1, 2]
Overall survival (OS) was significantly longer in patients with low, compared to patients with high, programmed cell death (PD)-1 expression (p = 0.021, log-rank), but OS was not significantly different based on PD-L1 expression (p = 0.155, log-rank) (Additional file 1: Fig. S1D, E)
Disease-free survival (DFS) and OS were not significantly different based on PD-L2 expression (p = 0.665, log-rank) (p = 0.595, logrank) (Fig. 3c) (Additional file 1: Fig. S1F)
Summary
Various immunosuppressive factors from cancer cells in the tumor microenvironment inhibit host immune responses to cancer [1, 2]. Immunotherapy is effective in malignant melanoma and renal cell carcinoma (RCC), but anti-tumor effects have been demonstrated in a variety of other cancers. Immune checkpoint inhibitor therapy, which turns anti-tumor T cells into effectors, has completely changed the role of cancer immunotherapy in clinical practice [5,6,7,8]. Breast cancer was not previously regarded as a tumor associated with abnormal immunity [9]. Immune checkpoint inhibitor therapy is expected to play a major role in the tailored treatment of breast cancer
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