Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.

Anaplastic lymphoma kinase (ALK) rearrangement is usually observed in patients with adenocarcinoma. Herein, we report a case of squamous cell carcinoma (SCC) with ALK rearrangement treated with alectinib. The patient was a 73-year-old woman without a smoking history. She consulted us with nonproductive cough and loss of appetite. Computed tomography scan revealed a mass in the left lower lobe of the lung. According to the pathological examinations, we diagnosed the tumor as SCC. Because the patient had never smoked, we searched for driver mutations and found that the tumor harbored ALK rearrangement. We began treatment with alectinib, and the tumor remarkably reduced in volume. No severe adverse events were observed. Although there are only few reports of SCC with ALK rearrangement, this case implies that clinicians should consider searching for driver mutations in patients with SCC when there are atypical findings or characteristics.

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