增强的口腔与侧侧淋巴结T细胞反应,与抗PD1在头癌中的疗效相匹配
Michihisa Kono1, Shin Saito2, Masahiro Rokugo2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Otolaryngology - Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
Oral oncology
|April 10, 2024
概括
头部和部状细胞癌 (HNSCC) 模型显示出不同的免疫反应. 与皮下模型相比,正位口腔瘤引起更强的T细胞激活和抗PD1治疗反应,影响临床前HNSCC研究.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 临床前癌症研究研究
背景情况:
- 了解头部和部状细胞癌 (HNSCC) 的组织特异性免疫反应对于解决免疫疗法耐药性至关重要.
- 临床前模型对于研究HNSCC免疫动态和治疗疗效至关重要.
研究的目的:
- 调查口腔和皮下侧侧瘤移植模型之间HNSCC特异性免疫反应的差异.
- 在不同的瘤微环境中比较免疫细胞动力学和对抗PD1治疗的反应.
主要方法:
- 使用的MOC1同基因小鼠口腔癌细胞系,包括表达SIINFEKL (MOC1OVA) 或ZsGreen (MOC1ZsGreen) 的版本.
- 在小鼠口腔粘膜 (口腔空间) 或皮下侧中注射细胞,分析瘤和瘤排水淋巴结 (TDLNs) 中的免疫细胞群.
- 对抗PD1阻塞疗法的评估反应.
主要成果:
- 与皮下侧侧瘤相比,正确的口腔瘤在瘤和TDLN中显示出更高的OVA特异性T细胞数量和激活 (PD1 +,CD69 +).
- 皮下侧侧瘤较大; CD8 枯竭使瘤重量在不同部位之间相等.
- 口服疫苗增强了TDLN淋巴细胞反应;口服TDLN中的cDC1显示增强了抗原吸收和共刺激,导致T细胞反应增加.
- 抗PD1阻塞拒绝了口腔MOC1瘤,但没有皮下侧翼MOC1瘤.
结论:
- орто托普口服和异型皮下HNSCC模型之间存在不同的免疫反应.
- 在TDLN中由传统的1型树突细胞 (cDC1) 进行原始化是关键的差异化因素.
- 这些发现对临床前HNSCC研究的设计和解释有重大影响.
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