Kim Young Ju, Rho Kyung Na, Jeong Saei, Lee Gil-Woo, Kim Hee-Ok, Cho Hyun-Ju, Bae Woo Kyun, Oh In-Jae, Lee Sung-Woo, Cho Jae-Ho
Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun 58128, Korea.
Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun 58128, Korea.
Immune Netw. 2023 Aug 21;23(4):e35. doi: 10.4110/in.2023.23.e35. eCollection 2023 Aug.
Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8 T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8 T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8 T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8 T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8 T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8 T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.
定义与T细胞分化相关的分子动力学，有助于我们更好地理解T细胞生物学，并为临床应用开辟新的可能性。在本研究中，我们调查了CD8 T细胞分化过程中CD5表达的动态变化，并探索了其潜在的临床用途。我们使用来自29名健康供体的外周血单核细胞（PBMC），观察到随着CD8 T细胞分化进程，CD5表达呈逐步下降趋势。有趣的是，我们发现CD5表达最初会因T细胞受体刺激而上调，但随着细胞增殖而减少，这可能解释了与分化相关的CD5下调现象。基于CD5的增殖依赖性下调，我们推测相对CD5表达可作为一种标志物，根据其增殖历史来区分异质性CD8 T细胞群体。为此，我们证明，与CD5表达较低的效应记忆CD8 T细胞相比，CD5表达较高的效应记忆CD8 T细胞表现出类似于分化程度较低细胞的表型和功能特征。此外，在对30例非小细胞肺癌患者的PBMC进行回顾性分析时，我们发现效应记忆T细胞中CD5表达较高的患者，其CD8 T细胞表型更接近分化程度较低的细胞，对免疫检查点抑制剂（ICI）治疗有较好的临床反应。这些发现突出了CD5表达动态变化作为CD8 T细胞分化状态指标的作用，并对ICI治疗预测性生物标志物的开发具有启示意义。
