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:Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?
Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?
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近年来,肿瘤微环境(TME)已成为癌症治疗干预的一个有前景的靶点。癌细胞高度依赖TME来生长和逃避免疫系统。在TME中,三个主要的细胞亚群相互对峙:癌细胞、免疫抑制细胞和免疫效应细胞。这些相互作用受到肿瘤基质的影響,肿瘤基质由细胞外基质、旁观者细胞、细胞因子和可溶性因子组成。TME因癌症发生的组织不同而差异很大,如实体瘤与血液癌症。多项研究表明,临床结局与TME免疫细胞浸润的特定模式之间存在相关性。近年来,越来越多的证据表明,非常规T细胞如自然杀伤T(NKT)细胞、黏膜相关恒定T(MAIT)细胞和γδ T细胞是实体瘤和血液癌症中促肿瘤或抗肿瘤TME承诺的关键参与者。在本综述中,我们将聚焦于γδ T细胞,尤其是Vγ9Vδ2 T细胞,讨论其特性、优势与劣势,作为血液癌症治疗干预的潜在靶点。
In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers.
Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers.
In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.
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