Cancer immunotherapy offers substantive benefit to patients with various tumour types, in some cases leading to complete tumour clearance. However, many patients do not respond to immunotherapy, galvanizing the field to define the mechanisms of pre-existing and acquired resistance. Interferon-γ (IFNγ) is a cytokine that has both protumour and antitumour activities, suggesting that it may serve as a nexus for responsiveness to immunotherapy. Many cancer immunotherapies and chemotherapies induce IFNγ production by various cell types, including activated T cells and natural killer cells. Patients resistant to these therapies commonly have molecular aberrations in the IFNγ signalling pathway or express resistance molecules driven by IFNγ. Given that all nucleated cells can respond to IFNγ, the functional consequences of IFNγ production need to be carefully dissected on a cell-by-cell basis. Here, we review the cells that produce IFNγ and the different effects of IFNγ in the tumour microenvironment, highlighting the pleiotropic nature of this multifunctional and abundant cytokine.

癌症免疫疗法为患有各种肿瘤类型的患者提供了实质性的好处，在某些情况下可以完全清除肿瘤。然而，许多患者对免疫疗法没有反应，这激发了该领域来定义预先存在的和获得性耐药的机制。干扰素-γ (IFNγ) 是一种具有促肿瘤和抗肿瘤活性的细胞因子，表明它可能作为免疫治疗反应的纽带。许多癌症免疫疗法和化学疗法诱导各种细胞类型产生 IFNγ，包括活化的 T 细胞和自然杀伤细胞。对这些疗法产生耐药性的患者通常在 IFNγ 信号通路中存在分子异常或表达由 IFNγ 驱动的耐药分子。鉴于所有有核细胞都能对 IFNγ 作出反应，需要逐个细胞仔细剖析 IFNγ 产生的功能后果。在这里，我们回顾了产生 IFNγ 的细胞以及 IFNγ 在肿瘤微环境中的不同作用，强调了这种多功能和丰富的细胞因子的多效性。