Effects of PRKCH on CD8<sup>+</sup>T cell function and melanoma immunotherapy

Renren YU; Hao LYU; Han CHU; Zheng JIN; Qingzhu JIA; Degao CHEN; Bo ZHU

doi:10.16016/j.2097-0927.202310088

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Effects of PRKCH on CD8⁺T cell function and melanoma immunotherapy

Basic Medicine | 更新时间：2026-01-09

- Effects of PRKCH on CD8⁺T cell function and melanoma immunotherapy
- Journal of Army Medical University Vol. 46, Issue 6, Pages: 556-566(2024)
- 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：
- 基金信息：
  
  the National Natural Science Foundation for Distinguished Young Scholars of China(81925030)
- DOI：10.16016/j.2097-0927.202310088
  CLC： R394.3;R730.51;R739.5
- Received：24 October 2023，
  
  Revised：2024-01-01，
  
  Published：30 March 2024
- 稿件说明：
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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：

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

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

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

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(

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

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

To explore the effect of PRKCH on CD8

T cell function and its role in predicting the efficacy of melanoma immunotherapy.

Methods

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

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

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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⁰

Effects of PRKCH on CD8+T cell function and melanoma immunotherapy

DOI：10.16016/j.2097-0927.202310088

摘要

Abstract

关键词

Keywords

references

Effects of PRKCH on CD8⁺T cell function and melanoma immunotherapy