Tumorigenesis embodies the formation of a heterotypic tumour microenvironment (TME) that, among its many functions, enables the evasion of T cell-mediated immune responses. Remarkably, most TME cell types, including cancer cells, fibroblasts, myeloid cells, vascular endothelial cells and pericytes, can be stimulated to deploy immunoregulatory programmes. These programmes involve regulatory inducers (signals-in) and functional effectors (signals-out) that impair CD8⁺ and CD4⁺ T cell activity through cytokines, growth factors, immune checkpoints and metabolites. Some signals target specific cell types, whereas others, such as transforming growth factor-β (TGFβ) and prostaglandin E₂ (PGE₂), exert broad, pleiotropic effects; as signals-in, they trigger immunosuppressive programmes in most TME cell types, and as signals-out, they directly inhibit T cells and also modulate other cells to reinforce immunosuppression. This functional diversity and redundancy pose a challenge for therapeutic targeting of the immune-evasive TME. Fundamentally, the commonality of regulatory programmes aimed at abrogating T cell activity, along with paracrine signalling between cells of the TME, suggests that many normal cell types are hard-wired with latent functions that can be triggered to prevent inappropriate immune attack. This intrinsic capability is evidently co-opted throughout the TME, enabling tumours to evade immune destruction.

肿瘤发生体现了异型肿瘤微环境 （TME） 的形成，在其众多功能中，能够逃避 T 细胞介导的免疫反应。值得注意的是，大多数 TME 细胞类型，包括癌细胞、成纤维细胞、髓样细胞、血管内皮细胞和周细胞，都可以受到刺激以部署免疫调节程序。这些程序涉及调节诱导剂（信号输入）和功能效应器（信号输出），它们通过细胞因子、生长因子、免疫检查点和代谢物损害 CD8⁺ 和 CD4⁺ T 细胞活性。一些信号靶向特定细胞类型，而其他信号，例如转化生长因子-β （TGFβ） 和前列腺素 E₂ （PGE₂），发挥广泛的多效性作用;作为信号输入，它们触发大多数 TME 细胞类型的免疫抑制程序，作为信号输出，它们直接抑制 T 细胞并调节其他细胞以加强免疫抑制。这种功能多样性和冗余性对免疫逃避型 TME 的治疗靶向构成了挑战。从根本上说，旨在消除 T 细胞活性的调节计划以及 TME 细胞之间的旁分泌信号传导的共同性表明，许多正常细胞类型具有可以触发以防止不适当的免疫攻击的潜在功能。这种内在能力显然在整个 TME 中被采用，使肿瘤能够逃避免疫破坏。