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:Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.
Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.
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在人类中,已鉴定出总共12种半乳糖凝集素。本综述探讨并讨论了它们的细胞内和细胞外生物学功能。这些半乳糖凝集素在控制肿瘤微环境(TME)内的免疫反应以及免疫细胞(包括不同亚群的T细胞、巨噬细胞和中性粒细胞)的浸润以对抗癌细胞方面发挥重要作用。
然而,这些浸润细胞也具有修复作用,并被癌细胞劫持用于促肿瘤活性。随着对半乳糖凝集素-3和-9免疫调节功能的进一步了解,其抑制剂,即GB1211和LYT-200,已被选为临床试验的候选药物。这些半乳糖凝集素抑制剂与当前免疫检查点抑制剂(ICIs)联合使用的方案也正在进行临床试验研究。通过其结合伴侣网络,半乳糖凝集素的抑制对CD8+细胞毒性T细胞、调节性T细胞(Tregs)、自然杀伤(NK)细胞和巨噬细胞产生广泛的下游效应,并发挥促炎作用,抑制T细胞耗竭以支持对抗癌细胞。本综述还纳入了其他半乳糖凝集素成员,以提供对未来潜在治疗候选药物的见解。
此外,还讨论了使用半乳糖凝集素及其抑制剂的陷阱和局限性,以认识其临床应用。
In humans, a total of 12 galectins have been identified. Their intracellular and extracellular biological functions are explored and discussed in this review. These galectins play important roles in controlling immune responses within the tumour microenvironment (TME) and the infiltration of immune cells, including different subsets of T cells, macrophages, and neutrophils, to fight against cancer cells.
However, these infiltrating cells also have repair roles and are hijacked by cancer cells for pro-tumorigenic activities. Upon a better understanding of the immunomodulating functions of galectin-3 and -9, their inhibitors, namely, GB1211 and LYT-200, have been selected as candidates for clinical trials. The use of these galectin inhibitors as combined treatments with current immune checkpoint inhibitors (ICIs) is also undergoing clinical trial investigations.
Through their network of binding partners, inhibition of galectin have broad downstream effects acting on CD8 + cytotoxic T cells, regulatory T cells (Tregs), Natural Killer (NK) cells, and macrophages as well as playing pro-inflammatory roles, inhibiting T-cell exhaustion to support the fight against cancer cells.
Other galectin members are also included in this review to provide insight into potential candidates for future treatment(s). The pitfalls and limitations of using galectins and their inhibitors are also discussed to cognise their clinical application.
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