Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
Cytokine Growth Factor Rev. 2023 Feb;69:73-79. doi: 10.1016/j.cytogfr.2022.08.004. Epub 2022 Sep 2.
Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. Of note, presence of FGL2 transforms low grade to high grade brain tumors via promoting Treg, macrophages, and perhaps stemness. Absence (knockout) of FGL2 in tumor cells (not in host cells) induces CD103 DC cells, which triggers tumor specific CD8 +T cell activity to reject brain tumor progression. Immunotherapies targeting FGL2 have shown great promise in improving survival time in murine models. In this article, we will summarize the biological function of FGL2 in immune and tumor cells.
脑肿瘤是癌症相关死亡的 10 大主要原因之一，由于其位置关键、遗传异质性和血脑屏障，治疗极具挑战性。靶向免疫疗法和免疫检查点阻断疗法的最新进展为脑肿瘤提供了替代治疗策略。纤维蛋白原样蛋白 2（FGL2）可诱导低级别胶质瘤向高级别神经胶质瘤转化，是一种 II 型膜蛋白，在宿主免疫细胞和肿瘤细胞中均高度表达。研究揭示了 FGL2 蛋白的多种形式，它们在诱导免疫耐受和避免肿瘤细胞免疫监视方面具有广泛的作用。值得注意的是，FGL2 的存在通过促进 Treg、巨噬细胞，也许还有干性，将低级别转化为高级别脑肿瘤。肿瘤细胞（而非宿主细胞）中 FGL2 的缺失（敲除）会诱导 CD103 DC 细胞，从而引发肿瘤特异性 CD8+T 细胞活性，拒绝脑肿瘤进展。针对 FGL2 的免疫疗法在改善小鼠模型的生存时间方面显示出巨大的潜力。在本文中，我们将总结 FGL2 在免疫细胞和肿瘤细胞中的生物学功能。
