Supporting this genetic interaction, CD44 positively correlated with PD-L1 expression at the mRNA and protein levels in primary tumor samples of TNBC and NSCLC patients.
For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need.
Total mRNA microarray analysis of TNBC cells showed that PDL-1 mRNA expression in HCC1937 and MDA-MD-436 cells was higher than in the other 2 TNBC cell lines, and that of MDA-MB-436 was higher than that of HCC1937.
Here, we report that human TNBCs molecularly stratified for high levels of PD-L1 (PD-L1<sup>High</sup>) showed significantly enriched expression of immune and cancer stemness pathways compared with those with low PD-L1 expression (PD-L1<sup>Low</sup>).
Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1<sup>+</sup>) TNBC, suggesting a functional association of FAK and immune checkpoints.
Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer.
In early 2019, the FDA granted the first approval of immune checkpoint therapy, targeting PD-L1 (Atezolizumab) in combination with chemotherapy for the treatment of patients with locally advanced or metastatic PD-L1 positive TNBC.
The humanized monoclonal antibody atezolizumab targets programmed death-ligand 1 and has demonstrated durable single-agent activity in a subset of metastatic triple-negative breast cancers.
There are also significant advancements in triple-negative breast cancer: By combining chemotherapy and immunotherapy, an advantage for overall survival was able to be demonstrated in a subgroup (immune cells PD-L1-positive).
Recently, we have seen 3 newly approved targeted therapies for TNBC, including the PARP inhibitors olaparib and talazoparib for germline BRCA mutation associated breast cancer (gBRCAm-BC) and most recently the checkpoint inhibitor, atezolizumab in combination with nab-paclitaxel for programmed death-ligand 1 (PD-L1+) advanced TNBC.
The Food and Drug Administration has lately approved atezolizumab, anti-programmed death ligand 1 (PD-L1), to be used together with nanoparticle albumin-bound (nab) paclitaxel in treating patients with triple negative breast cancer (BC) expressing PD-L1.
These drugs were selected based on the following: PTX is approved for TNBC; nintedanib combined with docetaxel has shown phase III clinical trial success, albeit in NSCLC; VEGF can act as local immunosuppressive factor; and PD-L1 antibody plus taxane therapy was recently reported to have encouraging phase III trial benefit in TNBC.
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.
In silico analysis of The Cancer Genome Atlas (TCGA) data shows that expression of histone lysine-specific demethylase 1 (LSD1) is inversely associated with the levels of cytotoxic T cell-attracting chemokines (C-C motif chemokine ligand 5 (CCL5), C-X-C motif chemokine ligand 9 and 10 (CXCL9, CXCL10)) and programmed death-ligand 1 (PD-L1) in clinical TNBC specimens.
Based on IMpassion130 clinical trial (NCT02425891), the Food and Drug Administration (FDA) has recently granted an accelerated approval for atezolizumab (TECENTRIQ®), a monoclonal antibody drug targeting PD-L1, plus chemotherapy (Abraxane; nab®-Paclitaxel) for the treatment of adults with PD-L1-positive, unresectable, locally advanced or metastatic TNBC.
Expert opinion: Atezolizumab, a novel immune checkpoint inhibitors targeting PD-L1, is an effective and well-tolerated treatment option for metastatic TNBC.
Among them, the programmed death ligand-1 (PD-L1) is of particular interest as it is expressed not only on T-cells, but also on other immune cells and on a large variety of cancer cells, such as breast cancer cells, considering its high expression in both ErbB2-positive and Triple Negative Breast Cancers.
PD-L1 expression was detected in 72% of the cases, and it expressed in a higher percentage and higher intensity in TILs than TCs in TNBC (p = 0.006 and 0.0005, respectively).
Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer.
Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes.
Combining the PD-L1 inhibitor atezolizumab with standard chemotherapy improves overall survival among patients with metastatic triple-negative breast cancer relative to chemotherapy alone.