Shulou(Shulou.com)06/01 Report--

This article is to share with you about what TMB means. The editor thinks it is very practical, so share it with you as a reference and follow the editor to have a look.

Tumor immunotherapy is a new type of treatment after traditional treatment, such as surgery, radiotherapy, chemotherapy and so on. Immune checkpoint inhibitors represented by PD-1/PD-L1 antibody have made good progress in the clinical treatment of melanoma, non-small cell lung cancer and other solid tumors.

However, the therapy also has the problem of low response rate, and only 10-30% of tumor patients can benefit from the therapy. In order to accurately screen the target group of immunotherapy, scientists have tried a variety of marker.

The most direct idea is to take the expression level of PD-L1 in tumor tissue as marker, and use immunohistochemical method to detect the expression of PD-L1 in tumor tissue. If the expression is high, it indicates that the patient may benefit from immunotherapy. However, there is no clear threshold to distinguish the expression level here, and clinical studies have found that patients with low or no expression of PD-L1 can also benefit from anti-PD-L1 therapy, indicating that the reliability of PD-L1 expression level as marker is open to question.

Tumor mutation load tumor mutation burden, referred to as TMB, represents the density of non-synonymous mutation distribution in the protein coding region. The total number of non-synonymous mutation sites in the protein coding region is divided by the total length of the protein coding region, in units of mutations/mb.

The occurrence of tumor is caused by somatic mutation, somatic cells undergo gene mutation under the action of carcinogenic factors, some mutant cells return to normal by DNA self-modification, some cells die, and some mutant cells express new antigens on their surface. Under normal circumstances, the immune system of the body can recognize these antigens and then identify these mutated cells through immune response, but tumor cells can achieve immune escape through abnormal expression of antigens or regulation of tumor microenvironment, continue to divide and grow, and form tumors.

The concept of TMB only targets non-synonymous mutations in the protein coding region, because only these mutations make it possible for tumor cells to produce new antigens. The higher the TMB, the more the type and number of new antigens produced by tumor cells, the higher the probability of being recognized by the immune system, and the greater the probability of killing these tumor cells after the immune checkpoint inhibitor activates the body's own anti-tumor immune response. Divide TMB into the following three levels

Low TMB: 1-5 mutations/mb

Intermediate TMB: 6-19 mutations/mb

High TMB: > 20 mutations/mb

A large number of literatures have reported that the level of TMB is related to the efficacy of PD1/PD-L1 antibody, tumor cells with higher TMB are more likely to be recognized by the immune system, and immunotherapy has a higher probability of effective in this patient. Calculating the TMB score of tumor patients can better guide clinical treatment.

From the definition of TMB, we can see that the most direct and effective method to calculate TMB is full exon sequencing. However, considering the experimental cycle and cost, there are also various panel designed according to targeted hot spot genes. This method has low cost and fast cycle, but the TMB score obtained is not as accurate as WES.

Thank you for reading! This is the end of this article on "what does TMB mean?". I hope the above content can be of some help to you, so that you can learn more knowledge. if you think the article is good, you can share it for more people to see!

Welcome to subscribe "Shulou Technology Information " to get latest news, interesting things and hot topics in the IT industry, and controls the hottest and latest Internet news, technology news and IT industry trends.