摘 要
近年来，癌症免疫治疗已成为肿瘤治疗领域的重要突破，其中免疫细胞的功能与调控机制是决定治疗效果的关键因素。本研究旨在系统探讨T细胞、NK细胞及巨噬细胞等主要免疫效应细胞在肿瘤微环境中的功能特性及其调控网络，以期为优化免疫治疗策略提供理论依据。研究采用单细胞RNA测序技术结合CRISPR-Cas9基因编辑系统，对临床样本和动物模型中的免疫细胞进行多维度分析。结果表明，肿瘤微环境中存在显著的免疫抑制性亚群分化，其中PD-1+Tim-3+耗竭性T细胞的扩增与肿瘤进展呈正相关；同时发现了一种新型的NK细胞亚群，其抗肿瘤活性显著高于传统NK细胞。通过构建基因调控网络模型，揭示了STAT3-IRF1信号轴在调节巨噬细胞极化中的核心作用。
关键词：癌症免疫治疗 肿瘤微环境 免疫细胞
Abstract
In recent years, cancer immunotherapy has become an important breakthrough in the field of tumor therapy, among which the function and regulatory mechanism of immune cells are the key factors in determining the therapeutic effect. The aim of this study was to systematically explore the functional characteristics and regulatory networks of major immune effector cells, including T cells, NK cells and macrophages, in the tumor microenvironment, in order to provide a theoretical basis for optimizing immunotherapy strategies. Studies used single-cell RNA sequencing combined with the CRISPR-Cas 9 gene editing system to perform multi-dimensional analysis of immune cells in clinical samples and animal models. The results showed that there were significant immunosuppressive subpopulation differentiation in the tumor microenvironment, in which the expansion of PD-1 + Tim-3 + depletive T cells was positively correlated with tumor progression; and a novel NK cell subset whose anti-tumor activity was significantly higher than that of conventional NK cells. A central role of the STAT 3-IRF 1 signaling axis in regulating macrophage polarization was revealed.
Keyword: Cancer immunotherapy tumor microenvironment immunocyte
目 录
1绪论 1
1.1研究背景与意义 1
1.2研究现状 1
1.3研究方法与创新点 2
2免疫细胞在肿瘤微环境中的作用机制 2
2.1 T细胞在肿瘤免疫中的功能特性 2
2.2NK细胞的抗肿瘤效应及其调控 3
2.3巨噬细胞在肿瘤免疫中的双重作用 3
3免疫检查点对免疫细胞的调控机制 4
3.1PD-1/PD-L1通路对T细胞的抑制作用 4
3.2CTLA-4对免疫细胞功能的调节 4
3.3新型免疫检查点的发现与应用前景 5
4基于免疫细胞的癌症治疗策略优化 6
4.1CAR-T细胞疗法的技术突破与挑战 6
4.2肿瘤疫苗与免疫细胞的协同作用 6
4.3联合疗法中免疫细胞的动态调控 7
5结论 7
参考文献 9
致谢 10
近年来，癌症免疫治疗已成为肿瘤治疗领域的重要突破，其中免疫细胞的功能与调控机制是决定治疗效果的关键因素。本研究旨在系统探讨T细胞、NK细胞及巨噬细胞等主要免疫效应细胞在肿瘤微环境中的功能特性及其调控网络，以期为优化免疫治疗策略提供理论依据。研究采用单细胞RNA测序技术结合CRISPR-Cas9基因编辑系统，对临床样本和动物模型中的免疫细胞进行多维度分析。结果表明，肿瘤微环境中存在显著的免疫抑制性亚群分化，其中PD-1+Tim-3+耗竭性T细胞的扩增与肿瘤进展呈正相关；同时发现了一种新型的NK细胞亚群，其抗肿瘤活性显著高于传统NK细胞。通过构建基因调控网络模型，揭示了STAT3-IRF1信号轴在调节巨噬细胞极化中的核心作用。
关键词：癌症免疫治疗 肿瘤微环境 免疫细胞
Abstract
In recent years, cancer immunotherapy has become an important breakthrough in the field of tumor therapy, among which the function and regulatory mechanism of immune cells are the key factors in determining the therapeutic effect. The aim of this study was to systematically explore the functional characteristics and regulatory networks of major immune effector cells, including T cells, NK cells and macrophages, in the tumor microenvironment, in order to provide a theoretical basis for optimizing immunotherapy strategies. Studies used single-cell RNA sequencing combined with the CRISPR-Cas 9 gene editing system to perform multi-dimensional analysis of immune cells in clinical samples and animal models. The results showed that there were significant immunosuppressive subpopulation differentiation in the tumor microenvironment, in which the expansion of PD-1 + Tim-3 + depletive T cells was positively correlated with tumor progression; and a novel NK cell subset whose anti-tumor activity was significantly higher than that of conventional NK cells. A central role of the STAT 3-IRF 1 signaling axis in regulating macrophage polarization was revealed.
Keyword: Cancer immunotherapy tumor microenvironment immunocyte
目 录
1绪论 1
1.1研究背景与意义 1
1.2研究现状 1
1.3研究方法与创新点 2
2免疫细胞在肿瘤微环境中的作用机制 2
2.1 T细胞在肿瘤免疫中的功能特性 2
2.2NK细胞的抗肿瘤效应及其调控 3
2.3巨噬细胞在肿瘤免疫中的双重作用 3
3免疫检查点对免疫细胞的调控机制 4
3.1PD-1/PD-L1通路对T细胞的抑制作用 4
3.2CTLA-4对免疫细胞功能的调节 4
3.3新型免疫检查点的发现与应用前景 5
4基于免疫细胞的癌症治疗策略优化 6
4.1CAR-T细胞疗法的技术突破与挑战 6
4.2肿瘤疫苗与免疫细胞的协同作用 6
4.3联合疗法中免疫细胞的动态调控 7
5结论 7
参考文献 9
致谢 10
