免疫系统有两种主要应对癌症的方式。首先，有预先编程的反应，涉及髓系细胞、固有淋巴细胞和类固有适应性淋巴细胞，它们或者居于早期恶性组织中，或者直接迁移到肿瘤，其次，有依赖抗原引发的应答，在次生淋巴器官中对适应性淋巴细胞进行引导后定位到肿瘤部位。转化生长因子-β（TGFβ）是最有效、具广泛调节性的细胞因子之一，它控制了从初级淋巴器官中的白细胞发育到在次生淋巴器官中进行引导以及在肿瘤中执行增效功能的肿瘤诱导的免疫反应的几乎每一阶段。TGFβ调控免疫细胞电路的复杂性，以及TGFβ信号在癌细胞和肿瘤基质细胞中的情境作用，需要使用严格的实验系统来全面复制人类癌症，如原位肿瘤模型，以揭示其中的免疫生物学原理。TGFβ在健康组织中的多样功能进一步复杂了针对TGFβ通路的癌症治疗的研究。在这里，我们将讨论TGFβ信号在肿瘤诱导的免疫反应中的情境复杂性，并解释如何理解此一点以指导基于机制的癌症免疫治疗的发展。© 2022. Springer Nature Limited.

The immune system responds to cancer in two main ways. First, there are prewired responses involving myeloid cells, innate lymphocytes and innate-like adaptive lymphocytes that either reside in premalignant tissues or migrate directly to tumours, and second, there are antigen priming-dependent responses, in which adaptive lymphocytes are primed in secondary lymphoid organs before homing to tumours. Transforming growth factor-β (TGFβ) - one of the most potent and pleiotropic regulatory cytokines - controls almost every stage of the tumour-elicited immune response, from leukocyte development in primary lymphoid organs to their priming in secondary lymphoid organs and their effector functions in the tumour itself. The complexity of TGFβ-regulated immune cell circuitries, as well as the contextual roles of TGFβ signalling in cancer cells and tumour stromal cells, necessitates the use of rigorous experimental systems that closely recapitulate human cancer, such as autochthonous tumour models, to uncover the underlying immunobiology. The diverse functions of TGFβ in healthy tissues further complicate the search for effective and safe cancer therapeutics targeting the TGFβ pathway. Here we discuss the contextual complexity of TGFβ signalling in tumour-elicited immune responses and explain how understanding this may guide the development of mechanism-based cancer immunotherapy.© 2022. Springer Nature Limited.