Shandong University Cancer Center, Shandong University, Jinan, Shandong, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
J Transl Med. 2024 Jan 5;22(1):27. doi: 10.1186/s12967-023-04839-4.
Tissue-resident memory T (T) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of T cells but we know little about it.
Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of T cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a T-based spatial immune signature (T-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α).
The density of T cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of T cell subsets was defined, including T (PD-1Tim-3T), T (PD-1Tim-3T), T (PD-1Tim-3T) and T (PD-1Tim-3T). The cytotoxicity of T was the strongest while that of T was the weakest. Compare with T and T, T and T had better infiltration and stronger interaction with cancer cells. The T-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63-3.60), P < 0.001] and showed a better performance than the TNM staging system for recurrence prediction. Furthermore, by CD103-related GSEA and mIF validation, we found a negative association between tumor angiogenesis and infiltration of T cells.
These findings reveal a significant heterogeneity in the functional status and spatial distribution of T cells, and support it as a biomarker for the prognosis of NSCLC patients. Regulating T cells by targeting tumor angiogenesis may be a potential strategy to improve current immunotherapy.
组织驻留记忆 T (T) 细胞可以驻留在肿瘤微环境中，被认为是免疫治疗的主要反应细胞。功能状态和空间分布的异质性可能导致 T 细胞作用的争议，但我们对此知之甚少。
通过多重免疫荧光（mIF）（CD8、CD103、PD-1、Tim-3、GZMB、CK），在 274 例接受根治性手术的 NSCLC 患者的组织中识别 T 细胞亚群的数量和空间位置。通过整合多种机器学习方法，我们构建了基于 T 细胞的空间免疫特征（T-SIS）来预测预后。此外，我们进行了 CD103 相关基因集富集分析（GSEA），并通过另一个 mIF 面板（CD8、CD103、CK、CD31、Hif-1α）验证了其发现。
T 细胞的密度与 PD-1、Tim-3 和 GZMB 的表达显著相关。定义了四种 T 细胞亚群，包括 T (PD-1Tim-3T)、T (PD-1Tim-3T)、T (PD-1Tim-3T) 和 T (PD-1Tim-3T)。T 的细胞毒性最强，而 T 的细胞毒性最弱。与 T 和 T 相比，T 和 T 具有更好的浸润性和更强的与癌细胞的相互作用。T-SIS 是无病生存期的独立预后因素[HR=2.43，95%CI（1.63-3.60），P<0.001]，并且在预测复发方面优于 TNM 分期系统。此外，通过 CD103 相关的 GSEA 和 mIF 验证，我们发现肿瘤血管生成与 T 细胞浸润之间存在负相关。
这些发现揭示了 T 细胞功能状态和空间分布的显著异质性，并支持其作为 NSCLC 患者预后的生物标志物。通过靶向肿瘤血管生成来调节 T 细胞可能是改善当前免疫治疗的一种潜在策略。
