Discussion
In this study, we uncovered a CD274 amplification, encoding for PD-L1, in a metastatic lesion of ITTC using NGS-based cancer mutation analysis. This amplification was also concordant with abundant PD-L1 expression on tumor cells, denoting a copy-number-dependent mechanism of PD-L1 overexpression in the metastatic ITTC. Only clinical case of metastatic ITTC has reported that pathological expression of PD-L1 was observed in 60% of tumor cells within a metastatic lesion of CASTLE localized to the parotid gland, and pembrolizumab was effective in controlling tumor progression without severe adverse events3. Tahara et al. also investigated PD-L1 expression on tumor cells in nine primary lesions of ITTC and confirmed PD-L1 expression in all samples 4. In our case, when the decision was taken to administer pembrolizumab, it was too late to improve the patient’s condition or prognosis. However, this accumulating evidence associated with CD274 copy number alterations and concordant expression of PD-L1 encouraged us to consider using an immune checkpoint inhibitor (ICI) such as pembrolizumab as a good systemic therapeutic option for treating metastatic ITTC.
Multiplex IHC and image flow cytometry have been employed for the pathological evaluation of tumor-immune microenvironment, yielding information on the types of immune cells that localize in tumor tissue5. As shown in Figure 2e, cytotoxic T cells infiltrating into the tumor nest or marginal area frequently expressed PD-1. These results indicate that the patient’s metastatic ITTC was characterized by high T cell infiltration and categorized as an immune-inflamed tumor that generally shows a better response to ICIs.