Liquid biopsy in immunotherapy

Many human tumors have a large number of DNA mutations, and past studies have demonstrated that the "tumor antigen" encoded by the mutated gene is a major driving force in the development of current cancer immunotherapy. Since the expression of the neoantigen is completely restricted to tumors, the development of a therapy that enhances the tumor antigen-specific T cell response is most welcome. However, because the vast majority of mutations in cancer patients (such as melanoma patients and lung cancer patients) are not shared in the foreseeable frequencies, this leads to the fact that the fact becomes more complicated, so that tumor rejection of the immune system is largely due to private antigens . How to develop new antigen-specific autologous T cell products? Scientists need fresh tumor materials, but this feat is difficult to achieve in a variety of tumors.

Recently, research published in the journal Nature Medicine showed a shortcut for obtaining tumor antigen-specific T cells. The researchers stated that they can accurately separate circulating blood from melanoma patients. As a result, they laid the foundation for new ideas for the treatment of cancer autoimmune cells with broad application potential.

In this study, the researchers used a method to determine the population of peripheral blood tumor-reactive T cells focused on the toxic CD8 T cell population. Earlier, the team had demonstrated that tumor-infiltrating T-cell-responsive tumors in melanoma patients are rich in PD-1 expressing T cells. To test whether peripheral blood T cells have such an effect, the researchers used flow cytometry to isolate CD8 T cell populations with or without PD-1 in the blood of cancer patients, and the researchers used deep sequencing to determine the tumor specificity of the corresponding patients. Sex mutations, artificial expression of mutated gene fragments in autologous dendritic cells.

By co-cultivating antigen-presenting cells with different CD8 T cell populations isolated from the patient's blood, the researchers found that PD-1–expressing Tcells in blood were not (or rarely) deficient. PD-1 T cells are reactive to antigens in individual tumors. Interestingly, the authors also showed that the tumor antigen specificity of PD cells expressing PD-1 in the blood cell compartment is very similar to that of the tumor itself.

A total of four melanoma patients participated in the study. The researchers isolated mutation-specific T cells from the blood of the three patients. How the results are applied to the general population of melanoma remains to be seen, not to mention for other types. Cancer. However, by showing the tumor response in the subset of PD-1 T cells, the study triggered a number of issues that warrant consideration.

First, how can these observations be transformed into subsets of T-lymphocytes: Does CD4 help T cells? This T-cell subtype contributes to initiating or maintaining the persistence of T cell responses, including tumor-targeting T cells. In addition, in contrast to CD8, CD4 helper T cells recognize tumor antigens that accompany DNA mutations, and there have been case reports that indicate the potential clinical utility of these cells. Therefore, it is important to understand whether PD-1 or other markers can be used to identify tumor-specific CD4 T cells in the blood chamber.

Second, the authors observed that tumor-specific CD8 T cells in the blood cavity express PD-1 in the absence of other markers or antibodies, then the question arises. What makes PD-1 special in this case? It is conceivable that the expression of PD-1 in circulating T cells reveals some of the activation signals that these cells have encountered, which is also a future research hotspot.