Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, USA.
Department of Biosciences, Rice University, Houston, Texas, USA.
Cancer Med. 2023 Mar;12(5):5590-5602. doi: 10.1002/cam4.5409. Epub 2022 Nov 16.
Immune checkpoint proteins play critical functions during the immune response to cancer and have been targeted by immune checkpoint blockade therapy. V-domain Ig suppressor of T cell activation (VSIR) is one of these immune checkpoint genes and has been investigated extensively in recent years due to its conflicting roles in cancer immunity. Specifically, in acute myeloid leukemia (AML), the prognostic value of VSIR is debated.
In both patient tumor samples and cancer cell lines we find that VSIR has the highest expression in AML out of all cancer types and, in AML, has the highest expression out of all other immune checkpoint genes. Survival analysis indicated that AML patients with higher VSIR expression have significantly shorter survival than those patients with lower expression, even within established AML subgroups (e.g., FAB subtypes). Importantly, VSIR expression is predictive of progression from myelodysplastic syndromes (MDS) patients into AML, suggesting its potential role during the very early stage of AML development and progression. In addition to AML, VSIR also demonstrates prognostic values in other cancer types, including multiple myeloma and mesothelioma.
In summary, our analyses revealed the prognostic value of VSIR and its potential as a target for immunotherapy, especially in AML.
免疫检查点蛋白在癌症免疫反应中发挥着关键作用,已经成为免疫检查点阻断治疗的靶点。V 结构域免疫球蛋白抑制 T 细胞激活因子(VSIR)是这些免疫检查点基因之一,近年来由于其在癌症免疫中的矛盾作用而受到广泛研究。具体来说,在急性髓系白血病(AML)中,VSIR 的预后价值存在争议。
在患者肿瘤样本和癌细胞系中,我们发现 VSIR 在所有癌症类型中的表达最高,在 AML 中,其表达高于所有其他免疫检查点基因。生存分析表明,VSIR 表达较高的 AML 患者的生存时间明显短于表达较低的患者,即使在已建立的 AML 亚组(例如,FAB 亚型)中也是如此。重要的是,VSIR 表达可预测骨髓增生异常综合征(MDS)患者向 AML 的进展,表明其在 AML 发展和进展的早期阶段可能具有潜在作用。除 AML 外,VSIR 在其他癌症类型中也具有预后价值,包括多发性骨髓瘤和间皮瘤。
总之,我们的分析揭示了 VSIR 的预后价值及其作为免疫治疗靶点的潜力,特别是在 AML 中。