Nowadays, immunotherapy has been able to improve treatment outcomes in many cancer patients, Including melanoma, etc others, But these therapies are effective for only a subset of patients, Numerous studies are looking at how to improve the patient's body response, Including a focus on how to enhance tumor-infiltrating lymphocytes (TILs, Function of the model-infiltrating lymphocytes), TILs are specialized immune cells in the tumors, Which can recognize and attack the cancer cells, But usually there are not enough TILs, Or it is not sufficient to use a robust response to persistently inhibit tumor growth and spread.
recently, Published in a study in the international journal Nature Cancer entitled "Fucosylation of HLA-DRB1 regulates CD4 + T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy", Scientists from the Mofitt Cancer Research Medium Institute have identified a relatively natural way to increase the number of TILs and antitumour activity, in the article, The investigator stated that, A non-toxic dietary plant sugar, L-trehalose (L-fucose), with higher levels in red and brown seaweed, or one that can increase the levels of TILs and promote the body's anti-tumor immunity, It also improves the therapeutic efficiency of immunotherapy. Although L-trehalose is found in many foods, it can also be synthesized by cells in the body by decomposition and transforming other molecules. It is very important for the immunity and development process of the body. Abnormal synthesis and use of L-trehalose are often associated with the occurrence of many diseases, including cancer.
Researchers Lau said, L-the overall level of trehalose in melanoma, and in the process of disease progression cells using L-trehalose will change, however, we found that through dietary supplement to increase the level of L-trehalose will inhibit tumor, and significantly increase the level of TILs, but also can enhance the efficacy of some immunotherapy in animal models, in the human body, melanoma in high levels of L-trehalose or associated with less invasive disease and patients with better response to therapy. The investigators want to determine the molecular mechanisms behind the increase of TILs and the induction of antitumor activity of the organism, In the last 7 years, They performed a series of experiments and for the first time, L-trehalose regulates the interaction between CD4 + T cells (class I TIL) and melanoma cells; In the mouse experiments, The investigators found that, Increase the levels of L-trehalose in tumor cells by oral administration of L-trehalose, Reduced tumor growth and increased the overall levels of TILs, Among the multiple immune cell types that make up the TILs, CD4 + T cells play a key role in mediating the increased levels of TILs and thus in suppressing melanoma during L-trehalose therapy, So the researchers identified a key molecular mechanism, Which can promote L-trehalose-mediated antitumor activity of CD4 + T cells.
When people think of sugar, they often think of glucose or sucrose, which are common sugars used by body cells to obtain energy. Unlike these sugars, L-trehalose is not used by cells to obtain energy, but to decorate proteins to fine tune their behavior and activities; researchers found that adding L-trehalose to HLA-DRB 1 protein promotes its localization to the surface of melanoma cells, thus inducing the anti-tumor immune cell activity mediated by CD4 + T cells. In addition to decorate the protein in the tumor cells, the researchers also found that L-trehalose can change the biology of CD4 + T cells and other immune cells and behavior, and it seems to be used to regulate the host body's immune function, these studies found that the use of L-trehalose to enhance the treatment of cancer patients immunotherapy is very important, therefore, later researchers further research found that oral L-trehalose can enhance immunotherapy drugs in the treatment of the curative effect of part of melanoma model.
Next, the researchers looked at tumor properties from three cancer centers, aiming to assess whether L-trehalose levels and the HLA-DRB 1 protein reflect the response to anti-PD-1 therapies, and found that patients who responded to PD-1 therapy tended to contain high levels of L-trehalose and L-trehalose-decorated HLA-DRB 1, suggesting that it may be used as a potential biomarker to help predict the response to immunotherapy. Our study identifies the molecular mechanism behind L-trehalose regulating an important interface between melanoma and immune cells, which could be used for therapeutic use by simply giving L-trehalose, and could also help researchers use sugar to fight cancer in the future, researcher Lau said.
Later researchers hope to translate their preclinical findings into more direct help to patients and determine how much L-trehalose can enhance the efficacy of immunotherapy, of course small clinical trials in melanoma patients; in conclusion, the findings show that fucosylation (fucosylation) may be the key mediator of antitumor immunity, the study also shows that L-trehalose as a powerful agent to safely increase the level of TILs and therapeutic efficacy in melanoma.
