肿瘤细胞MHC-I表达水平下调是肿瘤免疫逃逸的重要原因。我们最近发现在肿瘤细胞中敲除肿瘤蛋白SND1（已进行长期研究）后，细胞表面MHC-I分子明显增加，接种同源小鼠后瘤体内免疫细胞浸润数量显著增加；同时发现SND1不仅与Cnx和MHC-I分子重链(HC)结合，还与ER上参与ERAD途径的复合物结合（Derlin-1/Sec61/p97）。由此提出假设：肿瘤蛋白SND1阻挠了MHC-I分子在肿瘤细胞的抗原呈递。在肿瘤细胞ER中，SND1通过与Cnx和新生HC结合，阻止Cnx对HC的稳定作用，使HC不能进入正常成熟过程，而是被劫持进入ERAD途径，转运到胞浆中发生泛素化修饰而被降解。敲除细胞中SND1，HC能有效结合β2m形成成熟MHC-I分子呈递抗原肽到细胞表面，促进免疫细胞浸润（尤其是CD8+T），有效杀伤肿瘤细胞。该研究有助于深入探讨如何促进MHC-I/抗原呈递，改善肿瘤免疫微环境。

SND1, staphylococcal nuclease domain-containing protein 1, (also named p100 or Tudor-SN) is a multi-functional protein, which is recently identified as an oncoprotein promotes tumorigenesis by diverse mechanisms in different cancers. .Our group has been focusing on investigating the function of SND1 for many years. We discovered that SND1 forms a loop with SMAD family members and regulate reciprocally to promote breast cancer metastasis through TGF-β signaling pathway. Additionally, SND1 acts as an upstream regulator of SLUG, which is a key transcription factor in regulating the expression of E-CAD/N-CAD switch, resulting in the EMT in ovarian cancer cells. As a multi-functional protein, it is likely that SND1 regulates diversity signal pathways involved in proliferation or metastasis of different cancers..Defects in MHC-I antigen presentation represent a common feature of cancer and allow evasion from T cell recognition. Recently, we found that the expression level of MHC-I, on the membrane surface of tumor cells, was remarkably enhanced with knockout of oncoprotein SND1 (SND1-KO) in the tumor cells. Most importantly, after implanting the SND1-KO tumor cells in the homologous mice, the amount of infiltrated immune cells in the tumor tissue was significantly increased. Meanwhile, at the cellular level, we found that SND1 could associate with not only Cnx and nascent heavy chain (HC) of MHC-I molecule, but also the protein complexes (derlin-1/sec61/p97) involved in ERAD pathway. Based on above, we hypothesize that high expression of SND1 in tumor cells interrupted the MHC-I antigen presentation. In the ER of tumor cells, the association of SND1 and Cnx prevented it from stabilizing the nascent HC, as a result, HC cannot enter the normal maturation process, instead, it is hijacked into the ERAD pathway, which is degraded by the ubiquitin modification in the cytoplasm. With knockout of SND1 in tumor cells, HC can effectively combine with β2m to form mature MHC-I molecule and present antigen peptide to cell surface, consequently promote immune cell infiltration, especially CD8+T cells to effectively kill tumor cells.