Immunotherapy for tumors is very popular recently, especially melanoma, lung cancer and other tumors, and the effect of immunotherapy is surprisingly good. But on the whole, the proportion of patients who respond to tumor immunotherapy drugs is very low. Therefore, how to screen patients who may be sensitive to immunotherapy drugs before treatment is an urgent problem to be solved. Drugs at immune detection points inhibit the combination of PD- 1 and PD-L 1, so some studies think that immunohistochemical detection of the expression level of PD-L 1 in tumor cells can predict the curative effect. If the expression of PD-L 1 in tumor cells is low, it is not recommended to use immunodetection drugs. Keytruda, the immunotherapy drug of Merck 20 17, became the first approved trans-tumor drug, and the indication of the drug was written as being suitable for solid tumors with MMR deletion. MMR becomes a marker to predict the therapeutic effect of PD- 1. This topic was published in Science, which may provide high-level evidence for keytruda's indication writing.
MMR deletion predicts the therapeutic effect of PD- 1 inhibitor on solid tumor. In order to reach the conclusion mentioned in the title, it is necessary to design clinical studies and select patients with solid tumors according to the inclusion criteria. Regarding the standards of clinical trials of new drugs, it is speculated that most clinical trials of new drugs will select all patients whose current treatment schemes are ineffective. Therefore, if new drugs are confirmed to be effective, the push of guidelines is often not the first-line scheme, but the last recommendation.
According to MMR status, they were divided into MMR deletion group and MMR normal group. At present, the commonly used detection method is immunohistochemistry to detect the expression of MMR-related important proteins.
Drug intervention and curative effect evaluation: drug treatment was given at the immune checkpoint. After several cycles, the efficacy of chemotherapy was evaluated according to RECIST standard. The specific curative effect is divided into CR, PR, SD, PD and objective remission rate ORR. Secondary endpoints can even choose OS and DFS.
In the results presentation, table 1: clinical baseline data of selected patients, table 2: curative effect evaluation results, and figure 1: OS and DFS survival curves.
The above results are too thin to be scientific. It is better to study the molecular mechanism and how to induce the drug treatment effect of immune checkpoints after MMR deletion.
First, 12 patients with tumor tissue were selected, and the curative effect and survival time were evaluated after giving drugs at immune checkpoint. Then, a patient who received sensitive treatment was selected to study its preliminary mechanism at the molecular level.
The expression levels of MSH2, MSH6, PMS2 and MLH 1 protein were detected by immunohistochemistry. If the results show that any protein is completely missing, it is interpreted as dMMR, and if there is no protein missing, it is interpreted as pMMR.
All the patients in this group had received relevant treatment before, but the first-line treatment was ineffective, and the curative effect was evaluated as progressive patients. Finally, 86 patients were included, 12 kinds of tumors. All patients were in dMMR state after the test. Patients who did not participate in pMMR were compared as control group.
The evaluation criteria of curative effect were RECIST(V 1. 1) and solid tumor. * * * 78 patients were evaluated. The remaining 8 cases were not evaluated? Determine the specific evaluation time point? Eight patients were unable to evaluate the curative effect because they did not have image scanning after treatment 12 weeks.
This study is purely descriptive and there is no control group. The baseline characteristic table of selected patients is not included in the text, but can be seen in the attached table. The most important curative effect table is 1. But figure 1 is the highlight of the article, because the number of cases enrolled in the group is not too large, so the data of each case is displayed instead of being summarized into a table 1. Firstly, the proportion of tumor types in this group is displayed, and then the change of the maximum diameter measurement of each case is displayed in the form of waterfall chart. The swimming chart was used to show the follow-up time, medication, progress and death of each patient. As expected, the author also described the changes of PFS and OS, and described the data of PFS/OS median and PFS/OS for one year in detail.
Mechanism hypothesis: PD- 1 can induce the proliferation of tumor-specific T cells in peripheral blood, and the tumor tissue of dMMR contains functional MANA-specific T cells. MANAs: a new antigen associated with mutation
The top five MMR-prone tumors are endometrial cancer, gastric cancer, small intestine cancer, colorectal cancer and cervical cancer.