自发的新抗原特异性CD4+ T细胞对生长瘤的反应在功能和表型上是多样化的
Ryan Q Griswold1,2, Spencer E Brightman1,2, Karla Soria Zavala1
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, California, USA.
bioRxiv : the preprint server for biology
|April 8, 2025
概括
自然的CD4+T细胞对瘤的反应是多样化的,包括辅助型和调节型. 治疗性疫苗接种减少了调节性T细胞,并增强了抗瘤免疫力,即使具有低亲和性T细胞受体.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症免疫学 癌症免疫学
- T细胞生物学T细胞生物学
背景情况:
- CD4+ T 细胞通过多种功能子集调节细胞免疫力.
- 瘤生长可以通过抑制新抗原特异性CD4+T细胞反应来逃避免疫控制.
- 了解CD4+T细胞动态对于有效的癌症免疫疗法至关重要.
研究的目的:
- 描述天然的CD4+T细胞对免疫性较差的瘤 (SCC VII) 和验证的新抗原 (CTLCH129>Q) 的反应.
- 研究与α-PD-1结合的治疗性疫苗对新抗原特异性CD4+T细胞的影响.
- 探索T细胞受体 (TCR) 亲和力,功能子集和治疗疗效之间的关系.
主要方法:
- 使用特定于CTLCH129>Q/I-Ek的四聚体来跟踪新抗原特定的CD4+T细胞.
- 在瘤进展期间和治疗性疫苗接种后分析T细胞种群.
- 采用单细胞转录组分析来评估TCR多样性和功能子集.
主要成果:
- 自然的CD4+T细胞对生长瘤的反应表现出表型和功能多样性 (Th1,Tfh-like,Treg).
- 治疗性疫苗接种显著降低了新抗原特异性调节性T细胞 (Treg) 的频率.
- 在功能子集内,TCR亲和力有所变化,来自Treg细胞的低亲和力TCR在采用细胞疗法 (ACT) 中表现出治疗疗效.
结论:
- 新抗原特异性CD4+ T细胞反应在瘤生长过程中具有功能多样性.
- 免疫治疗干预,包括接种和α-PD-1,调节T细胞子集并增强抗瘤免疫力.
- TCR亲和力不是CD4+T细胞功能的唯一决定因素;即使是低亲和力的TCR也可以为治疗成功做出贡献.
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