Abstract:Dendritic cells (DCs) were first isolated from mouse spleen lymph nodes by Steinman and Cohn in 1973. They are named after dendritic or pseudopod-like processes on the surface of cells when they mature in vivo. DC is currently known professional antigen presenting cells that activate primary T cells. Studies have shown that DC plays a key role in immune response and plays a two-way role in transplant immunity. On the one hand, DC presents donor antigens and activation signals to receptor T cells to induce the occurrence of rejection; on the other hand, some DCs have immunomodulatory effects, which induce the body's immune tolerance to autologous and foreign antigens. Therefore, the use of DC immunomodulatory effects to induce specific immune tolerance has become one of the research hotspots in the current transplantation field. In recent years, immunotherapy of tumors has attracted much attention, and it has become the fourth treatment method after tumor surgery, radiotherapy and chemotherapy. Dendritic cells (DC) are the most powerful antigen-presenting cells (APCs) in the body and are the only APCs that can activate the initial immune response. Therefore, the preparation and application of DC tumor vaccines have become a research hotspot in tumor immunotherapy. At present, the most important work of the tumor research is to culture DC in vitro, sensitize with antigen or antigen polypeptide, and then sensitize the DC to the tumor-bearing host for immunotherapy. Clinical studies have shown that DC immunotherapy induces a specific antigenic immune response that is safe for the human body. The advantages of DC in identifying tumor cells, stimulating the collective immune response, and fighting tumor cells are prominent in immunotherapy, which can eliminate malignant tumors or even cancer stem cells that fail to cure chemotherapy. Most systems of immunotherapy are implemented by DC. This article will focus on the development of dendritic cells and other applications and prospects in the treatment of cancer.Keywords: dendritic cells, tumor, development status

u Overview of dendritic cells

Dendritic cells (DCs) are the most potent cells in the three specialized antigen presenting cells in the body. Since mature DCs form many protrusions that resemble dendrites in nerve cells, they are named dendritic cells. It can be said that such cells are the dividing lines between natural immunity and specific immunity. They rely on innate receptors to uniquely recognize antigens and present processed antigenic peptides to T cells that perform specific immunity; or, like follicular dendritic cells, immobilize unmodified protein antigens in their cell membranes. The surface is recognized by nearby B cells.

DC is mainly differentiated by common stem cells (HSC) under the action of different basal cells and their secreted cytokines. The specific effects are mainly cytokines such as stem cell growth factor, monocyte colony stimulating factor, and interleukin. Under the stimulation of these different cytokines, HSCs are gradually differentiated into different kinds of dendritic cells and distributed to various locations in the body. There are several ways to classify DCs. According to their cytological and biochemical properties, they can be divided into two types, one is the migration of dendritic cells, and the other is the colonization of dendritic cells. If divided according to their growth period, it can be divided into two types: immature DC cells and mature DC cells. For DC, its process of uptake of antigen and presentation to lymphocytes is separated in time. Immature DC cells have a strong ability to uptake and process antigens. Although it can express low levels of FcR, it does not have the function of presenting antigens to lymphocytes; mature DC cells express high levels of MHC class I and MHC class II molecules (follicular dendrites located in lymphoid tissues) Except for cells). Thus, it has a strong antigen-presenting ability, but at the cost of losing the ability to take up and treat antigens. The most typical feature is that such cells no longer have the ability to phagocytose particles.

u How does DC resist tumors?

Antigen presentation of DC

DC is the most effective and powerful full-time APC in the body, capturing antigens with tumor therapeutic effects, and processing the Ag information to T and B lymphocytes, thereby triggering a series of specific immune responses. DC can not only capture soluble Ag through receptor-mediated endocytic pathway and strong liquid phase swallowing function, but also store captured Ag for a long time, thus maintaining T memory stem cells clone and serum antibody levels; Complex receptors such as MHC-II on the surface of DC specifically bind to processing and presentation; DC is not only the most effective APC involved in the production of MHC class II molecularly restricted immune responses to exogenous protein Ag, but also for other types. Ag also has a powerful presentation.

DC and immune activation

Through cell adhesion, TCR recognition of Ag and co-stimulatory signals, DC directly activates APC of unsensitized T cells, DC transmits two types of signals to T cells, one is DC MHC molecule The Ag complex binds to the TCR of the T cell to provide a first activation signal; the other is that the adhesion molecule on the DC surface binds to the T cell surface ligand, providing a second activation signal (ie, a costimulatory signal) that further activates the T cell. DC plays an important role in the growth of B cells and the secretion of immunoglobulin. Although it is also APC, DC has a higher expression of MHC and co-stimulatory factors and can produce a large amount of IL_12 and IL-18 to proliferate B cells. The number is increased by 3 to 6 times, which can directly stimulate the production of antibodies.

u DCs and malignant lymphoma

Studies have shown that inoculation of idiotypic proteins or expression of idiotype-type DCs from DCs by lymphocytes is used in lymphoma, and it has been found that CTLs stimulated with DCs loaded with idiotype-type proteins exhibit specific, CD-mediated MHC- Class I restricted cytotoxic effects against autologous, light chain idiotypes. Stimulation with uniquely transfected DCs caused only mild natural killer cell activity. This indicates that there are specific CTLs in lymphoma patients, and that these cells do not require viable lymphoma cells, and transduction of foreign antigens can induce the production of unique MHC class I restricted CTLs.

u The foreground of dendritic cells

The use of DC cell vaccine to treat tumors is encouraging from the experimental and clinical results. Studies have shown that DC cell vaccine-based immunotherapy is one of the most valuable and promising methods in today's cancer treatment. However, there are still various challenges in making DC cell vaccines truly a clinically widely applicable cancer treatment method. The best method for preparing DC cells and the optimal procedure for such vaccination have not been clarified until now. These problems have a major impact on the clinical application of DC cell vaccines. In addition, a potential threat is that if these vaccines are returned for a long period of time, the body's autoimmune response may be induced. Excessive reinfusion may lead to depletion of T cells, which may cause a decline in immune function, or may also trigger autoimmune diseases. If these problems cannot be effectively solved, it will certainly hinder the application of DC cells in tumor therapy. It is believed that with the in-depth study and exploration of DC cells and their mechanism of action, DC cell vaccines can be applied in clinical field more broadly, safely and effectively as a powerful method for treating tumors.