T 细胞功能的正向调节剂可预测低级别神经胶质瘤的预后和微环境特征。
Positive regulators of T cell functions as predictors of prognosis and microenvironment characteristics of low-grade gliomas.
机构信息
PET-CT Center, Chenzhou First People's Hospital, Chenzhou, Hunan, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Front Immunol. 2023 Jan 16;13:1089792. doi: 10.3389/fimmu.2022.1089792. eCollection 2022.
BACKGROUND
Low-grade gliomas (LGG) are one of the most prevalent types of brain cancers. The efficacy of immunotherapy in LGG is limited compared to other cancers. Immunosuppression in the tumor microenvironment (TME) of LGG is one of the main reasons for the low efficacy of immunotherapy. Recent studies have identified 33 positive regulators of T cell functions (TPRs) that play a critical role in promoting the proliferation, activity, and functions of multiple immunocytes. However, their role in the TME of LGG has not been investigated. This study aimed to construct a risk model based on these TPRs and to detect the significance of immunotypes in predicting LGG prognosis and immunotherapy efficacy.
METHODS
A total of 688 LGGs and 202 normal brain tissues were extracted from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases. The NMF R package was used to identify TRP-related subtypes. The TPR prognostic model was established using the least absolute shrinkage and selection operator (LASSO) algorithm to predict the overall survival of LGG samples.
RESULTS
The Subtype 2 patients had worse survival outcomes, suppressed immune function, and higher immune cell infiltration. A risk regression model consisting of 14 TPRs was established, and its performance was validated in CGGA325 cohorts. The low-risk group exhibited better overall survival, immune microenvironment, and immunotherapy response, as determined the TIDE algorithm, indicating that increasing the level of immune infiltration can effectively improve the response to immunotherapy in the low-risk group. The risk score was determined to be an independent hazard factor (p<0.001) although other clinical features (age, sex, grade, IDH status, 1p19q codel status, MGMT status, and accepted radiotherapy) were considered. Lastly, high-risk groups in both cohorts revealed optimal drug responses to rapamycin, paclitaxel, JW-7-52-1, and bortezomib.
CONCLUSIONS
Our study identified two distinct TPR subtypes and built a TPR signature to elucidate the characteristics of T cell proliferation in LGG and its association with immune status and prognosis. These findings shed light on possible immunotherapeutic strategies for LGGs.
背景
低级别胶质瘤（LGG）是最常见的脑癌类型之一。与其他癌症相比，免疫疗法在 LGG 中的疗效有限。LGG 肿瘤微环境（TME）中的免疫抑制是免疫疗法疗效低下的主要原因之一。最近的研究已经确定了 33 种 T 细胞功能的正调节剂（TPR），它们在促进多种免疫细胞的增殖、活性和功能方面发挥着关键作用。然而，它们在 LGG 的 TME 中的作用尚未得到研究。本研究旨在构建基于这些 TPR 的风险模型，并检测免疫类型在预测 LGG 预后和免疫治疗效果方面的意义。
方法
从癌症基因组图谱（TCGA）、中国胶质瘤基因组图谱（CGGA）和基因型组织表达（GTEx）数据库中提取了 688 例 LGG 和 202 例正常脑组织。使用 NMF R 包来识别 TPR 相关亚型。使用最小绝对收缩和选择算子（LASSO）算法建立 TPR 预后模型，以预测 LGG 样本的总生存期。
结果
亚型 2 患者的生存结局较差，免疫功能受到抑制，免疫细胞浸润较高。建立了一个由 14 个 TPR 组成的风险回归模型，并在 CGGA325 队列中进行了验证。低风险组的总生存期、免疫微环境和免疫治疗反应更好，通过 TIDE 算法确定，这表明增加免疫浸润水平可以有效地提高低风险组对免疫治疗的反应。尽管考虑了其他临床特征（年龄、性别、分级、IDH 状态、1p19q 共缺失状态、MGMT 状态和接受放疗），风险评分仍被确定为独立的危险因子（p<0.001）。最后，两个队列的高风险组均对雷帕霉素、紫杉醇、JW-7-52-1 和硼替佐米表现出最佳的药物反应。
结论
本研究确定了两种不同的 TPR 亚型，并构建了 TPR 特征来阐明 LGG 中 T 细胞增殖的特征及其与免疫状态和预后的关系。这些发现为 LGG 的可能免疫治疗策略提供了思路。
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