論文 - 詳細
| RRC ID | 86024 |
|---|---|
| 著者 | Hirose K, Otsu H, Masuda T, Saeki H, Tobo T, Hosoda K, Matsumoto C, Tatsumi T, Ikehara T, Ofuchi T, Higuchi S, Abe T, Nakano Y, Hashimoto M, Nakanoko T, Oki E, Yoshizumi T, Mimori K. |
| タイトル | Cytotoxic Anti-tumor Drugs and Tumor-Associated Macrophages Synergistically Surge PD-L1 Expression in Esophageal Squamous Cell Carcinoma. |
| ジャーナル | Ann Surg Oncol |
| Abstract |
BACKGROUND:Programmed cell death ligand 1 (PD-L1) expression within the tumor microenvironment (TME) is a key predictor of immune checkpoint inhibitor (ICI) efficacy in esophageal squamous cell carcinoma (ESCC). Chemotherapy-induced modulation of the TME, particularly through some immune cells including tumor-associated macrophages, may influence PD-L1 expression and impact treatment outcomes. PATIENTS AND METHODS:A retrospective analysis was conducted on 241 patients with ESCC, with or without preoperative chemotherapy, who underwent curative esophagectomy at our single institute, Kyushu University. Propensity score matching accounted for clinical factors. Immunohistochemistry evaluated PD-L1, PD-L2, HLA class I, CD8, and CD68 expression. RNA sequencing data from 92 patients with ESCC from the cancer genome atlas underwent TME deconvolution analysis. In vitro experiments utilized ESCC cell lines, THP-1-derived macrophages, and chemotherapeutics (5-fluorouracil, cisplatin, and docetaxel) to explore their effects on PD-L1 expression. RESULTS:Chemotherapy-treated patients showed significantly elevated PD-L1 expression in tumor and interstitial cells. These patients also had increased peritumoral CD68-positive macrophage accumulation, correlating positively with tumor PD-L1 expression. In silico analysis pinpointed polarized macrophages as the primary immune cells linked to PD-L1 upregulation in the TME. In vitro, PD-L1 expression in tumor cells rose post-chemotherapy and further increased when co-cultured with activated macrophages, indicating a synergistic effect. CONCLUSIONS:Cytotoxic drugs and tumor-associated macrophages surge PD-L1 expression in ESCC, likely through cytokine-mediated pathways. This interaction suggests that integrating cytotoxic chemotherapy with macrophage activation may boost immune checkpoint inhibitor (ICI) efficacy, offering a viable strategy to optimize immunotherapy in ESCC. |
| 巻・号 | 32(10) |
| ページ | 7860-7873 |
| 公開日 | 2025-10-1 |
| DOI | 10.1245/s10434-025-17710-1 |
| PII | 10.1245/s10434-025-17710-1 |
| PMID | 40619486 |
| MeSH | Aged Antineoplastic Agents* / pharmacology Antineoplastic Combined Chemotherapy Protocols* / therapeutic use B7-H1 Antigen* / genetics B7-H1 Antigen* / metabolism Biomarkers, Tumor / metabolism Cisplatin / administration & dosage Docetaxel / administration & dosage Esophageal Neoplasms* / drug therapy Esophageal Neoplasms* / metabolism Esophageal Neoplasms* / pathology Esophageal Squamous Cell Carcinoma* / drug therapy Esophageal Squamous Cell Carcinoma* / metabolism Esophageal Squamous Cell Carcinoma* / pathology Esophagectomy Female Fluorouracil / administration & dosage Follow-Up Studies Humans Male Middle Aged Prognosis Retrospective Studies Survival Rate Tumor Cells, Cultured Tumor Microenvironment / drug effects Tumor-Associated Macrophages* / drug effects Tumor-Associated Macrophages* / immunology Tumor-Associated Macrophages* / metabolism Tumor-Associated Macrophages* / pathology |
| IF | 4.061 |
| リソース情報 | |
| ヒト・動物細胞 | TE-1(RCB1894) TE-4(RCB2097) TE-5(RCB1949) TE-6(RCB1950) TE-9(RCB1988) TE-10(RCB2099) TE-14(RCB2101) |