Accumulating evidence indicates that aberrant signalling stemming from genetic abnormalities in cancer cells has a fundamental role in their evasion of antitumour immunity. Immune escape mechanisms include enhanced expression of immunosuppressive molecules, such as immune-checkpoint proteins, and the accumulation of immunosuppressive cells, including regulatory T (T_reg) cells, in the tumour microenvironment. Therefore, T_reg cells are key targets for cancer immunotherapy. Given that therapies targeting molecules predominantly expressed by T_reg cells, such as CD25 or GITR, have thus far had limited antitumour efficacy, elucidating how certain characteristics of cancer, particularly genetic abnormalities, influence T_reg cells is necessary to develop novel immunotherapeutic strategies. Hence, T_reg cell-targeted strategies based on the particular characteristics of cancer in each patient, such as the combination of immune-checkpoint inhibitors with molecularly targeted agents that disrupt the immunosuppressive networks mediating T_reg cell recruitment and/or activation, could become a new paradigm of cancer therapy. In this Review, we discuss new insights on the mechanisms by which cancers generate immunosuppressive networks that attenuate antitumour immunity and how these networks confer resistance to cancer immunotherapy, with a focus on T_reg cells. These insights lead us to propose the concept of ‘immuno-genomic precision medicine’ based on specific characteristics of cancer, especially genetic profiles, that correlate with particular mechanisms of tumour immune escape and might, therefore, inform the optimal choice of immunotherapy for individual patients.

越来越多的证据表明，癌细胞遗传异常产生的异常信号在其逃避抗肿瘤免疫方面发挥着重要作用。免疫逃逸机制包括肿瘤微环境中免疫抑制分子（例如免疫检查点蛋白）的表达增强，以及免疫抑制细胞（包括调节性 T (T _{reg ) 细胞）的积累。}因此，T _reg细胞是癌症免疫治疗的关键靶点。鉴于迄今为止针对主要由 T _reg细胞表达的分子（例如 CD25 或 GITR）的疗法的抗肿瘤功效有限，阐明癌症的某些特征（特别是遗传异常）如何影响 T _reg细胞对于开发新的免疫治疗策略是必要的。因此，基于每位患者癌症特定特征的 T _{reg细胞靶向策略，例如将免疫检查点抑制剂与破坏介导 T reg}细胞募集和/或激活的免疫抑制网络的分子靶向药物相结合，可能会成为一种有效的治疗策略。癌症治疗的新范式。在这篇综述中，我们讨论了关于癌症产生削弱抗肿瘤免疫力的免疫抑制网络的机制的新见解，以及这些网络如何赋予癌症免疫治疗耐药性，重点是 T _reg细胞。这些见解促使我们根据癌症的具体特征，特别是基因谱，提出“免疫基因组精准医学”的概念，这些特征与肿瘤免疫逃逸的特定机制相关，因此可能为个体患者提供免疫治疗的最佳选择。 。