New study finds key mechanism by which NK cells lose anti-tumor function

The body develops various defense mechanisms against tumor growth, many of which are inherent in the cell. The most obvious of these is the regulation of cells through apoptosis mechanisms, so that cells that are physiologically dysfunctional or have suffered some kind of injury or stress die. The pRb pathway and DNA repair system are involved in preventing the formation of initial cancer cells in a similar way.

In addition to these cell-and tissue-specific mechanisms, mammals have another defense system-the immune system. The immune system efficiently finds and removes foreign infectious pathogens from our tissues. In the second half of the 20th century, one of the focuses of cancer research was whether the immune system could recognize cancer cells as outsiders and eliminate them.

In fact, the body's immune system does have multiple levels of anti-tumor immunity, and data in this area are rapidly accumulating. Compared with other fields, although the field of tumor immunology and cancer research in the basic concept is still a lot of controversy. But investing more time and energy in one area will greatly expand our understanding of the etiology of tumors and help us find ways to treat human tumors.
Anti-tumor immunity is an ancient concept. In 1957, Burnet and Lewis Thomas made inferences about the immune system to monitor the occurrence of tumors in tissues, and clearly proposed and described the concept of tumor immune surveillance for the first time.

At that time, it was believed that infectious microorganisms such as bacteria, viruses, and fungi had strong immunogenicity. They could stimulate the body's immune response and eventually be completely eliminated by different branches of the immune system. By analogy, the body's immune system is likely to monitor the emergence of cancer cells in the body's tissues at all times. Once the cancer cells are identified, it is logical that the immune system treats the cancer cells as if they were foreign invaders, gaining proliferation and forming life-threatening tumors. Destroy them before.

Support for the theory of immunosurveillance comes from studies in mice deficient in the IFN-γ gene, where knockout mice for the IFN-γ receptor are 10-20 times more sensitive to tumor induction by the chemical carcinogen 3-MC. When 3-MC induces the formation of transformed cells in a host with normal immune function, those transformed cells with strong immunogenicity can be effectively eliminated by the host, and only those cancer cells with weak immunogenicity can survive and further grow.

These observations suggest that the immune system of these mice plays an active role in the recognition of tumors and the process of their expressed antigens, and the active intervention of the immune system on the tumor phenotype is called immunoediting. Immune editing can be seen as a type of Darwinian theory of natural selection, where selection pressure comes from the immune system's direct attack on nascent tumors.

In addition, the tumor can enter the third mode. Tumors can be kept under constant surveillance (without being destroyed) by the adaptive immune system, growing indolently in the body to form small tumors with no obvious symptoms. Such tumor cells proliferate slowly, have antigenicity, can be cleared by immune cells, and the clearance rate is the same as that of tumor cells, so that the tumor enters a long-term, surface stable equilibrium state.

This delicate balance can be disrupted in at least two ways. One is that oncology will inhibit the expression of its more immunogenic antigens, so that it evades immune recognition and clearance, so that the tumor cells with weak antigenicity suddenly grow in an outbreak. Alternatively, certain components of the acquired immune system are damaged or destroyed, and immune-mediated tumor suppression is reduced, leading to progressive growth of tumors that have been dormant for months or even some years.