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PRKCH的表达对CD8+T细胞功能及黑色素瘤免疫治疗的影响
Effects of PRKCH on CD8+T cell function and melanoma immunotherapy
- 陆军军医大学学报 2024年46卷第6期 页码：556-566
- 作者机构：
1.325000 浙江 温州，温州医科大学附属第一医院肿瘤科
2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院肿瘤科
3.610064 成都，四川大学生命科学学院生长代谢衰老研究中心
4.201318 上海，上海仁东医学检验所有限公司
5.400037 重庆，肿瘤免疫治疗重庆市重点实验室
- 作者简介：
[朱波，E-mail: bo.zhu@tmmu.edu.cnZHU Bo, E-mail: bo.zhu@tmmu.edu.cn
- 基金信息：国家杰出青年科学基金资助项目(81925030)
DOI：10.16016/j.2097-0927.202310088
中图分类号： R394.3;R730.51;R739.5收稿：2023-10-24，
修回：2024-01-01，
纸质出版：2024-03-30
- 稿件说明：
移动端阅览
余忍忍, 吕浩, 储涵, 等. PRKCH的表达对CD8+T细胞功能及黑色素瘤免疫治疗的影响[J]. 陆军军医大学学报, 2024,46(6):556-566.
Renren YU, Hao LYU, Han CHU, et al. Effects of PRKCH on CD8+T cell function and melanoma immunotherapy[J]. Journal of Army Medical University, 2024, 46(6): 556-566.
余忍忍, 吕浩, 储涵, 等. PRKCH的表达对CD8+T细胞功能及黑色素瘤免疫治疗的影响[J]. 陆军军医大学学报, 2024,46(6):556-566. DOI： 10.16016/j.2097-0927.202310088.
Renren YU, Hao LYU, Han CHU, et al. Effects of PRKCH on CD8+T cell function and melanoma immunotherapy[J]. Journal of Army Medical University, 2024, 46(6): 556-566. DOI： 10.16016/j.2097-0927.202310088.
摘要
目的
2
探讨PRKCH表达对CD8
+
T细胞功能的影响及其在黑色素瘤免疫治疗效果预测中的作用。
方法
2
运用Kaplan-Meier法分析黑色素瘤免疫治疗队列以及肿瘤基因组图谱(TCGA)数据中PRKCH在黑色素瘤中的表达及其与总生存期(overall survival，OS)的相关性。利用单细胞RNA测序(single-cell RNA-sequencing，scRNA-seq)数据分析PRKCH的细胞表达群体，利用蛋白质互作网络(protein-protein interaction networks，PPI)和基因集富集分析(gene set enrichment analysis，GSEA)评估PRKCH诱导抗肿瘤免疫应答的机制。利用逆转录病毒过表达和敲减PRKCH，检测小鼠CD8
+
T细胞功能。利用B16-OVA小鼠黑色素瘤模型验证PRKCH过表达的OT-1 CD8
+
T细胞对肿瘤生长的影响。
结果
2
在黑色素瘤免疫治疗队列和TCGA数据中，高水平的PRKCH显著延长患者OS(
P
<
0.05)。scRNA-seq分析显示PRKCH可以在T细胞表达。PPI、GSEA和scRNA-seq分析显示PRKCH的高表达与更多的细胞毒性和记忆性T细胞形成相关。过表达和敲减PRKCH分别增强和减少CD8
+
T细胞的增殖及IFN-γ、Granzyme B的表达。过表达P RKCH增强OT-1 CD8
+
T细胞的肿瘤抑制能力。
结论
2
PRKCH增强CD8
+
T细胞抑制肿瘤进展的能力，并可以用于预测黑色素瘤免疫治疗效果。
Abstract
Objective
2
To explore the effect of PRKCH on CD8
+
T cell function and its role in predicting the efficacy of melanoma immunotherapy.
Methods
2
Kaplan-Meier survival analysis was used to evaluate the correlation between PRKCH and overall survival (OS) in melanoma immunotherapy cohorts and The Cancer Genome Atlas (TCGA) data. Single-cell RNA-sequencing (scRNA-seq) data were employed to analyze the cellular expression of PRKCH. Protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were applied to analyze the mechanism of PRKCH-induced anti-tumor immune responses. After retroviral overexpression and knockdown of PRKCH
the function of mouse CD8
+
T cells was examined. The anti-tumor effect of PRKCH overexpressed OT-1 CD8
+
T cells was assessed using B16-OVA mouse melanoma model.
Results
2
A positive correlation was observed between PRKCH expression and OS in the melanoma ICI cohorts and SKCM data in TCGA. scRNA-seq data indicated that PRKCH was expressed in T cells. PPI
GSEA and scRNA-seq data showed that PRKCH may induce more cytotoxic and memory T cells. PRKCH overexpression and knockdown enhanced and decreased CD8
+
T cell proliferation and IFN-γ and Granzyme B expression
respectively. Additionally
PRKCH overexpression enhanced the tumor inhibition of OT-1 CD8
+
T cells.
Conclusion
2
PRKCH enhances the anti-tumor effect of CD8
+
T cells
and can be used to predict the efficacy of immunotherapy in melanoma.
关键词
Keywords
references
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