Natural killer cell， NK

　　Natural killer cell

　　The first line of defense against cancer in the human body

　　NK cells are derived from the English word Natural Killer cell, which is a core cell of the human body's innate immune cells and is considered the "first line of defense" for human health.

　　NK cells are important immune cells in the body. They are not only related to anti-tumor， anti-viral infection and immune regulation， but also participate in the occurrence of hypersensitivity and autoimmune diseases in some cases. They can identify target cells and kill mediators. NK cells patrol the blood at all times and can respond quickly to kill diseased cells， including cancer cells， virus-infected cells and inflammatory cells.

　　The main principle of NK cell anti-tumor

　　NK cells are derived from bone marrow lymphoid stem cells. Their differentiation and development depend on the bone marrow and thymus microenvironment. They are mainly distributed in the bone marrow, peripheral blood, liver, spleen, lungs and lymph nodes.

　　01. Perforin

　　Perforin is a medium for killing target cells released by cytoplasmic granules of killer cells such as NK， CTL， and LAK. Perforin purified from cytoplasmic granules can dissolve a variety of tumor cells in vitro， and anti-perforin antibodies can inhibit killing activity. IL-2 can increase the transcription of perforin gene. IL-6 can promote the induction effect of IL-2 on perforin gene transcription. Serine esterase may have the effect of activating perforin.

　　02.NK cytotoxic factor

　　NK cells can release soluble NK cytotoxic factor. There are NKCF receptors on the surface of target cells. After NKCF binds to target cells， it can selectively kill and lyse target cells.

　　03.TNF

　　Activated NK cells can release TNF-α and TNF-β (LT). TNF kills target cells by： ① changing the stability of target cell lysosomes， resulting in the leakage of multiple hydrolases; ② affecting cell membrane phospholipid metabolism; ③ changing target cell sugar metabolism to reduce the pH in tissues; ④ and activating target cell endonucleases， degrading genomic DNA and causing programmed cell death. The process of cell death caused by TNF is significantly slower than the process of perforin lysing cells.

　　04.ADCC

　　NK cells， macrophages and neutrophils expressing IgGFc receptors kill target cells by binding to the Fc segment of IgG antibodies that have bound to the surface of target cells such as virus-infected cells and tumor cells.

　　05. Secretion of cytokines

　　Activated NK cells can synthesize and secrete a variety of cytokines， which play a role in regulating immunity and hematopoiesis and directly killing target cells.

　　The main role of NK cells

　　The most commonly used method of NK cell therapy is to obtain human peripheral blood mononuclear cells， and stimulate them with antibodies and cytokines in vitro， resulting in the activation and proliferation of NK cells in vitro， and then infusing them back into cancer patients. The greatly increased number of activated NK cells exerts unprecedented anti-tumor activity in the body， assisting other therapies to achieve the purpose of killing tumors.

　　Role · 1

　　Prevent cancer and accurately screen cancer cells

　　Unlike other immune cells, NK cells can accurately "screen" and destroy cancer cells that are "missed" by other immune cells.

　　Our human body produces about 6，000 cancer cells every day， and the innate immune cells， mainly NK cells， are responsible for "monitoring" these cancer cells day and night.

　　Function· 2

　　Fighting cancer， natural inherent immune function

　　When NK cells patrol the body， they constantly contact other cells. Whether NK cells kill these cells depends on the balance of signals from the activating receptors and inhibitory receptors on the surface of NK cells. NK cells have a broad spectrum of anti-tumor effects and have a killing effect on almost all common types of cancer cells， including lung cancer， breast cancer， liver cancer， lymphoma， esophageal cancer， etc.

　　In the latest research, NK cells have been widely used in various cancers, including: blood system tumors, neuroblastoma, ovarian tumors, rhabdomyosarcoma, breast cancer, gastric cancer, etc.; and achieved good results in these studies.

　　The process of NK cells killing cancer cells

　　Compared with healthy people， the activity of NK cells in cancer patients is usually significantly reduced. Therefore， effectively increasing the number of NK cells and improving cell activity are considered to be important factors that can directly enhance the immunity of cancer patients.

　　Effect · 3

　　Anti-aging： Clear zombie cells and extend lifespan

　　Human aging is caused by cell aging. As we age， cells that stop growing accumulate in the body and form useless "zombie cells"， which will cause aging-related diseases over time. Such as senile degenerative diseases， cardiovascular diseases， malignant tumors， tissue/organ fibrosis， diabetes， osteoporosis， autoimmune diseases， etc. These diseases have very high morbidity and mortality rates and are important factors in human death. As the core cells of innate immune cells， NK cells are the absolute main force in clearing senescent cells.

　　NK cell immunotherapy

　　Stay away from cancer

　　Stay away from cancer is the common wish of mankind. As immune cell therapy matures, this wish has finally begun to become a reality. Even if the NK cells in our body fail, we can rely on NK cell therapy to "stand up" again.

　　· 1 · Re-transfuse NK cells to strengthen immunity

　　For ordinary people who want to stay away from cancer. Timely replenishing the number of NK cells in the body and improving and stabilizing the internal environment of the body is a convenient method of enhancing immunity in clinical use today. By collecting our own immune cells， culturing them in vitro， and expanding their number to a certain level， they are then re-transfused into the human body.

　　· 2 · NK cell therapy， hope for conquering solid tumors

　　CAR-NK has more tumor-killing pathways and is more suitable for attacking tumor cells with diverse antigen expression (solid tumors often have diverse antigen expression). For the human body， studies have found that it has fewer toxic side effects and better anti-tumor effects. Since it does not secrete inflammatory factors such as IL-1 and IL-6， it will not even trigger a cytokine storm. Therefore， CAR-NK is also regarded as one of the most anticipated engineered cell therapies after CAR-T.

　　The emergence of immunotherapy has given people hope for conquering cancer. In the past decade， immunotherapy has become one of the hottest areas of cancer research. It not only gives cancer patients hope of "cure"， but also brings cancer treatment into a new era. In the future， as NK cell research is further developed， it will play a greater role in the management of human health.