Department of Pediatric Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
Pediatr Surg Int. 2022 Nov 28;39(1):6. doi: 10.1007/s00383-022-05292-y.
Immunotherapy may improve the poor prognosis of high-risk neuroblastoma. Programmed cell death-1 (PD-1) is expressed in several cancers. The tyrosine hydroxylase MYCN (TH-MYCN) transgenic mouse model is widely used in neuroblastoma research, but detailed information on its immunological background is lacking. Therefore, we studied the immunological tumor microenvironment and tumor cell surface antigen expression in homozygote and hemizygote mice and effects of antibody therapy against PD-1.
CD4, CD8, CD11b, and CD11c expression in immune cells from retroperitoneal lymph nodes and spleen was analyzed by flow cytometry. Tumor cell surface antigen expression was confirmed, and data from homozygote and hemizygote mice were compared. Effects of anti-PD-1 antibody were evaluated.
CD4-, CD8-, CD11b-, and CD11c-positive cells were not significantly different in homozygote and hemizygote mice, and CD11b- and CD11c-positive cells were identified in the tumor microenvironment in both. Tumor cells expressed PD-1, and anti-PD-1 antibody had anti-tumor effects and significantly reduced the percentage of living tumor cells in cultures after 2 h.
The immunological background is similar in homozygote and hemizygote TH-MYCN transgenic mice, and both have PD-1-positive tumor cells. Anti-PD-1 antibody suppresses tumor growth. This mouse model may be a useful for studying immunotherapy of neuroblastoma.
免疫疗法可能改善高危神经母细胞瘤的预后不良。程序性细胞死亡受体-1（PD-1）在几种癌症中表达。酪氨酸羟化酶 MYCN（TH-MYCN）转基因小鼠模型广泛用于神经母细胞瘤研究，但缺乏其免疫学背景的详细信息。因此，我们研究了同型和杂合子小鼠的免疫肿瘤微环境和肿瘤细胞表面抗原表达，以及抗 PD-1 抗体治疗的效果。
通过流式细胞术分析腹膜后淋巴结和脾脏免疫细胞中 CD4、CD8、CD11b 和 CD11c 的表达。确认肿瘤细胞表面抗原的表达，并比较同型和杂合子小鼠的数据。评估抗 PD-1 抗体的效果。
同型和杂合子小鼠的 CD4+、CD8+、CD11b+和 CD11c+细胞无明显差异，且两者的肿瘤微环境中均存在 CD11b+和 CD11c+细胞。肿瘤细胞表达 PD-1，抗 PD-1 抗体具有抗肿瘤作用，可显著减少培养 2 小时后存活肿瘤细胞的比例。
TH-MYCN 转基因同型和杂合子小鼠的免疫学背景相似，两者均有 PD-1 阳性肿瘤细胞。抗 PD-1 抗体抑制肿瘤生长。该小鼠模型可能有助于研究神经母细胞瘤的免疫疗法。
