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.