SLC1A5, SLC7A5, SLC3A2 and immune cell markers CD3, CD8, FOXP3, CD20 and CD68, in addition to PD1 and PDL1, were assessed by using immunohistochemistry on TMAs constructed from a large BC cohort (n = 803).
PubMed and Embase were searched for all original English-language articles published before January 30, 2019; all articles reported the predictive and prognostic implications of PD-L1<sup>+</sup> in breast cancer.
Our results show that PDL1 protein expression is a predictive biomarker of pCR and a prognostic factor of DFS in breast cancer patients and HR-positive subgroups.
Hormone receptor-positive/HER2-negative (HR<sup>+</sup>/HER2<sup>-</sup>) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy.
Taken together, our data support a bispecific antibody approach to enhance the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade in Her2-positive metastatic breast cancers.
The findings of D'Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration-approved antibodies to CTLA4 and PD-1/PD-L1.
This study highlighted the importance of stromal types and stromal PD-L1 status in determining clinical outcomes in patients with breast cancer, and suggested that stromal type classification might be readily incorporated into routine clinical risk assessment following curative resection or optimal therapeutic design.
This review provides clinicians with an overview of the available clinical evidence regarding PD-L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD-L1 implementation as a clinically useful tool for breast cancer management.
SIGNIFICANCE: These findings show that inhibition of Aurora A facilitates an anticancer immune microenvironment, which can suppress tumor progression and enhance anti-PD-L1 therapy in breast cancer.<i>See related commentary by Rivoltini et al., p. 3169</i>.
Interestingly, BRCA1-, but not BRCA2-, deficient breast cancers were associated with increased expression of PD-L1 and PD-1, higher abundance of tumour-infiltrating immune cells, and enrichment of T cell-inflamed signature.
Single-drug therapies with monoclonal antibodies against programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have shown little efficacy in patients with metastatic breast cancer, in part because of the low number of tumour-infiltrating lymphocytes in most breast cancers.
However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non-small-cell lung cancer because of its limited expression of PD-L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid-derived suppressor cells (MDSCs).
Among the breast cancer subtypes, evaluation of ICB has been of greatest interest in triple-negative breast cancer (TNBC) due to its immunogenicity, as evidenced by the presence of tumor-infiltrating lymphocytes and elevated PD-L1 expression relative to other subtypes.
Our preclinical data suggest that anti-PD-L1 plus sunitinib may warrant further investigation as an adjuvant therapy for RCC, while anti-PD-L1 may be improved by combining with chemotherapy in the neoadjuvant but not the adjuvant setting of treating breast cancer.
Besides PD-L1 expression, a variety of potential biomarkers are under investigation for predicting immunotherapy efficacy in breast cancer, such as tumor-infiltrating lymphocytes, gene signatures, tumor mutational burden, microsatellite instability, and gut microbiome.