Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but exhibit variable efficacy and relapse and can induce autoimmunity. Tumor necrosis factor (TNF) receptor 2 (TNFR2) is a signaling molecule found on the surface of a subset of potent regulatory T cells (T_regs) that can activate the proliferation of these cells through nuclear factor kappa B (NF-κB). TNFR2 is also abundantly expressed on the surface of many human tumors. We propose that blocking TNFR2 might target abundant TNFR2⁺ tumor-infiltrating T_regs and directly kill TNFR2-expressing tumors. We also posit that TNFR2 inhibitors might potentially constitute safer and more targeted alternatives to ICI cancer treatment because the expression of TNFR2 on immune cells, concentrated in the tumor microenvironment of various cancers, appears to be more selective than that of checkpoint molecules.

免疫检查点抑制剂（ICIs）已彻底改变了癌症治疗方法，但显示出可变的疗效和复发能力，并可以诱导自身免疫。肿瘤坏死因子（TNF）受体2（TNFR2）是一种信号分子，存在于强大的调节性T细胞（T _reg s）子集的表面，可通过核因子kappa B（NF-κB）激活这些细胞的增殖。 。TNFR2在许多人类肿瘤的表面上也大量表达。我们建议阻断TNFR2可能靶向丰富的TNFR2 ⁺肿瘤浸润性T _reg并直接杀死表达TNFR2的肿瘤。我们还假设，TNFR2抑制剂可能构成ICI癌症治疗的更安全和更有针对性的替代方法，因为TNFR2在免疫细胞上的表达集中在各种癌症的肿瘤微环境中，似乎比检查点分子更具选择性。