Department of Radiation Oncology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Anticancer Res. 2023 Oct;43(10):4691-4700. doi: 10.21873/anticanres.16665.
BACKGROUND/AIM: Development of multidisciplinary therapies including immune checkpoint inhibitors for esophageal squamous cell carcinoma (ESCC) requires a clear understanding of immunological responses induced by chemotherapy with/without radiotherapy in the tumor microenvironment.
This is a retrospective analysis of paired pretreatment biopsy samples and surgically resected tumor samples of 49 patients who underwent radical surgery for ESCC with/without neoadjuvant therapy at Fukushima Medical University Hospital. The cohort included 30 patients treated with neoadjuvant chemotherapy (NAC), 11 treated with neoadjuvant chemoradiotherapy (NACRT), and eight who underwent surgery alone and did not receive neoadjuvant antitumor therapy. Chemotherapy included fluoropyrimidine- and platinum-based agents in all treated patients, and radiotherapy included 40 or 42 Gy administered in 20 or 21 fractions. Expression of CD8, human leukocyte antigen (HLA) class I-ABC, PD-L1, PD-L2, CEACAM-1, LSECtin, and p-STAT1, were determined using immunohistochemistry.
The frequency of tumor-infiltrating CD8 T cells was significantly increased by NAC (p<0.05), and the expression of HLA class I-ABC on tumor cells was significantly increased by NAC and NACRT (p<0.05). Furthermore, the ESCC cells expressed PD-L1, PD-L2, and CEACAM-1, whereas the expression of PD-L1 on ESCC cells was significantly correlated with the expression of p-STAT1 in ESCC cells (p<0.05).
NAC and NACRT induced both positive and negative immunological responses in patients with ESCC. These results may be a part of basis for multidisciplinary therapy including immune checkpoint inhibitors for patients with advanced ESCC.
背景/目的：为了开发包括免疫检查点抑制剂在内的多学科治疗方法，需要清楚地了解化疗联合/不联合放疗在肿瘤微环境中引起的免疫反应。
这是一项回顾性分析，纳入了 49 名在福岛医科大学医院接受根治性手术治疗的食管鳞癌（ESCC）患者的术前活检样本和手术切除肿瘤样本。该队列包括 30 名接受新辅助化疗（NAC）的患者、11 名接受新辅助放化疗（NACRT）的患者以及 8 名仅接受手术治疗且未接受新辅助抗肿瘤治疗的患者。所有接受治疗的患者均接受氟嘧啶和铂类药物化疗，放疗剂量为 40 或 42 Gy，分割 20 或 21 次。采用免疫组织化学法检测 CD8、人类白细胞抗原（HLA）I 类 ABC、PD-L1、PD-L2、CEACAM-1、LSECtin 和 p-STAT1 的表达。
NAC 可显著增加肿瘤浸润性 CD8 T 细胞的频率（p<0.05），并显著增加肿瘤细胞 HLA 类 I 类 ABC 的表达（p<0.05）。此外，ESCC 细胞表达 PD-L1、PD-L2 和 CEACAM-1，且 ESCC 细胞 PD-L1 的表达与 ESCC 细胞中 p-STAT1 的表达显著相关（p<0.05）。
NAC 和 NACRT 可诱导 ESCC 患者产生正向和负向免疫反应。这些结果可能是为晚期 ESCC 患者提供包括免疫检查点抑制剂在内的多学科治疗方法的部分依据。
