Sci Adv: I don't blame T-cells for not being active! Chinese scientists have found that cancer cells actively degrade MHC-1 molecules, so it's no wonder T-cells don't recognize cancer cells.

!---- There are many tricks for cancer cells to escape the immune system, such as the immune checkpoints we are already familiar with.But from the results of clinical studies, immunocheckpoint inhibitors targeting PD-1/L1 or CTLA-4 can improve the survival of some patients, but not all patients are able to respond.clearly, there are more immune mechanisms behind us.recently, scientists at Tianjin Medical University published new findings in the journal Nature Advances.they found that cancer cells were able to "hijack" the main tissue-compatible complex 1 molecule (MHC-1) through a protein SND1 and force them into the degradation process.this reduces the ability of CD8-T cells to recognize cancer cells and eventually allows them to escape the immune system."in a variety of solid tumors, including melanoma, lung cancer, breast cancer, kidney cancer, prostate cancer and bladder cancer, about 20%-60% of tumor immune escape is caused by MHC-1 defects, CD8-T cell recognition, the specific mechanism varies according to the cancer species.presents sND1 as a new cancer protein that detects its high expression in almost all tumors, as presented in the study today.SND1 is a conservative protein that is common in mammals and has a variety of physiological functions, and previous studies have shown that SND1 regulates the differentiation and migration of cancer cells, as well as the transformation of epithelial-interstitial, but it is not clear what effect SND1 has on tumors.in order to study the role of SND1 in tumor proliferation, the researchers first made a purification analysis of cancer cells, identified a group of proteins associated with the action of SND1, including a group of proteins related to the endothelial network (ER), such as human white blood cell antigen-A (HLA-A), VCP, SEC61A, nuclear glycoprotein protein L7a (RPL7A) and so on.it is well known that HLA-A is part of human MHC-1, and mHC-1 molecule is the key to antigen delivery, so the relationship between HLA-A and SND1 quickly attracted the attention of researchers.based on structural simulation, the interaction interface is between the SN3 region of SND1 and the A1 and A3 of HLA-A, which indicates that SND1 can interact with the immature HLA-A.that is, SND1 was ready to do something about THE HLA-A when it was just produced and did not yet form the MHC-1 full body.What did SND1 do? Considering that HLA-A is synthesized and matured in the internal network, the researchers first speculated that the effects of SND1 and HLA-A also occurred on the endoscosinal network, and that SND1 was mentioned earlier as associated with many ER proteins.through immunoassay, the researchers found that SND1 is a protein that is fixed to the endothelial mesh by binding SEC61A, which can be "captured" as soon as HLA-A is synthesized.knockout of SND1, it was observed that the level of HLA-A on the surface of cancer cells increased, while the level of HLA-A decreased in SND1 over-expression cells.but although the protein levels change, but the mRNA levels are not significantly changed, combined with previous findings, the researchers speculated that SND1 may not have prevented the synthesis of HLA-A, but induced the degradation of HLA-A. normally, the protein can also be transferred from the endothelial mesh to the cytoplasm for ubiquitinization, which in turn opens the endoscopic network-related degradation (ERAD) process, and SND1 is the forced introduction of HLA-A into THE ERAD to degrade it. researchers continued their experiments in mice, knocking SND1 out of melanoma and colon gland cancer cells, respectively, and resulted in SND1 missing tumors growing significantly slower than normal tumors in control, and tumors of smaller size and weight. analysis showed that the number of CD8-T cells in tumors missing from SND1 was also higher, although there was no difference in the proportion of PD-1-positive T cells. this means that the absence of SND1 can promote antigen presentation, increase CD8 plus T cell immersion, enhance anti-tumor immunity. the researchers also screened data from the TIMER database and the PrognoScan database and found that SND1 expression was indeed negatively correlated with T-cell immersion in melanoma and colon adenocarcinoma, and that SND1 expression significantly affected the prognosis of melanoma and colorectal cancer. these results, SND1 may be a potential therapeutic target for enhancing the immune response and inhibiting tumor growth. .