RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.
Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.
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三阴性乳腺癌(TNBC)是一种异质性乳腺癌亚型,以侵袭性临床行为和不良预后为特征。与 TNBC 相关的免疫景观常显示出高免疫原性。因此,鉴于目前除常规化疗外可用的治疗选择有限,已在不同癌症类型中证明其疗效的免疫治疗可能是 TNBC 的一种有前景的策略。天冬氨酸蛋白酶组织蛋白酶 D(cath-D)是一种肿瘤细胞相关细胞外蛋白,具有促肿瘤活性,是不良预后的标志物,也是 TNBC 中基于抗体的治疗的靶点。本评论提供了不同形式的抗 cath-D 抗体开发的概要/叙述性总结,它们在恢复抗肿瘤免疫中的关键作用,特别是通过激活肿瘤浸润NK 细胞,以及它们对癌细胞和基质癌相关成纤维细胞的双重抗肿瘤作用,表明鉴于当前关于 TNBC 的临床知识,它们具有临床使用价值。
Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype characterized by aggressive clinical behavior and poor prognosis. The immune landscape associated with TNBC often reveals high immunogenicity.
Therefore, immunotherapy, which has demonstrated its efficacy in different cancer types, could be a promising strategy for TNBC, given the limited therapeutic options currently available besides conventional chemotherapy. The aspartic protease cathepsin D (cath-D) is a tumor cell-associated extracellular protein with protumor activity, a marker of poor prognosis, and a target for antibody-based therapy in TNBC.
This commentary provides a synopsis/narrative summary of the development of anti-cath-D antibodies in different formats, their key roles in restoring the antitumor immunity, particularly via activation of tumor-infiltrating natural killer cells, and their dual antitumor effects on cancer cells and stromal cancer-associated fibroblasts, suggesting their interest for clinical use in the light of the current clinical knowledge on TNBC.
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