1. PD‐L1 and PD‐L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma
- Author
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Kazuo Okadome, Noriko Yasuda-Yoshihara, Taisuke Yagi, Tasuku Toihata, Takatsugu Ishimoto, Masayuki Watanabe, Yoshifumi Baba, Daichi Nomoto, Hiroshi Sawayama, Naoya Yoshida, Katsuhiro Ogawa, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Yoshihiro Komohara, and Hideo Baba
- Subjects
Cancer Research ,Esophageal Neoplasms ,medicine.medical_treatment ,B7-H1 Antigen ,Metastasis ,Cell Line, Tumor ,PD-L1 ,Biomarkers, Tumor ,medicine ,Humans ,Lymph node ,Cisplatin ,Chemotherapy ,biology ,business.industry ,General Medicine ,Esophageal cancer ,Programmed Cell Death 1 Ligand 2 Protein ,medicine.disease ,Neoadjuvant Therapy ,medicine.anatomical_structure ,Oncology ,Fluorouracil ,Lymphatic Metastasis ,Cancer research ,biology.protein ,Biomarker (medicine) ,Esophageal Squamous Cell Carcinoma ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Immune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD-L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD-L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD-L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD-L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD-L1/L2 expression and PD-L1/L2-related pathways in vitro. We also examined PD-L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD-L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD-L2 expression showed no significant difference between patient groups. Cisplatin increased PD-L1 expression in cancer cell lines in vitro, but decreased PD-L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD-L1 and PD-L2 expression. PD-L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD-L1/L2 expression may be altered by preoperative chemotherapy, and PD-L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one-time evaluation is not sufficient to evaluate PD-L1/L2 expression as a biomarker in esophageal cancer.
- Published
- 2021