Clinical experience of immune checkpoint inhibitor for a metastatic jejunal cancer patient with a high tumor mutational burden and low expression of programmed death-ligand 1

Recent data showed that DNA mismatch repair deficiency can be a predictive biomarker for a favorable response of immune checkpoint inhibitors regardless of tumor type due to give rise to high tumor mutational burden (TMB) and microsatellite instability (MSI). Loss-of-function mutations of a specific tumor suppressor gene can also lead to good response to immunotherapy. Herein, we report a case exhibiting good response to pembrolizumab in a jejunal adenocarcinoma patient with low programmed death-ligand 1 (PD-L1) expression. A 67-year-old man underwent surgical resection followed by adjuvant chemotherapy. After 10 months, he was treated with palliative chemotherapy due to hepatic and pulmonary metastases. However, palliative chemotherapy did not have any effect whatsoever. Based on genetic testing results of high TMB and high MSI in the resected primary tumor, pembrolizumab treatment was performed. After the three cycles of treatment, all metastatic lesions shrank remarkably. Considering the mechanism of immune checkpoint inhibitors, this case establishes the importance of genetic markers as TMB and MSI rather than PD-L1 expression by the prediction of their anti-tumor activities..