Language
Country/Area
No result found
Did you know how cancer immunosurveillance changed our understanding of cancer in 1957?
The history of cancer research is full of discoveries and breakthroughs, and within this picture, the role of the immune system has gradually become the focus of scientists' attention. In 1957, scientists Burnet and Thomas proposed the theory of cancer immune surveillance. This concept not only changed the way we understand the formation of cancer, but also laid the foundation for subsequent cancer immunotherapy.
Cancer immune surveillance is a key biological process that promotes host protection by inhibiting the development of nascent tumor cells.
According to this theory, lymphocytes can be regarded as "sentinels" responsible for identifying and destroying cancerous cells that continue to emerge. This perspective has sparked an in-depth discussion on how the immune system suppresses tumorigenesis and highlights the importance of continuous immune monitoring in cancer prevention and treatment.
Discovery of tumor antigens
Tumor cells may express tumor antigens, which can be recognized by the immune system and trigger an immune response. Tumor antigens can be divided into tumor-specific antigens (TSA) and tumor-associated antigens (TAA). The former is an antigen that only appears in tumor cells, while the latter is also present in healthy cells, but the expression level is different in tumor cells.
Tumor-specific antigens such as the E6 and E7 proteins are derived from the human papillomavirus and are specific to certain cancers such as cervical cancer.
For example, AFP (alpha-fetoprotein) is a tumor-associated antigen produced by hepatocellular carcinoma, and CEA (carcinoembryonic antigen) is found in ovarian and colon cancers. The study of these antigens forms the basis of immunotherapy, allowing us to develop treatments that target specific antigens.
The process of immunoediting
In the interaction between the immune system and tumor cells, immunoediting is a key phenomenon. This process is divided into three stages: elimination, balance and escape.
These three stages are often called the "three E's" of immunoediting
In the elimination phase, the immune system effectively recognizes and eliminates tumor cells, thereby inhibiting tumor growth. Over time, some tumor cells may acquire new mutations that allow them to evade the immune system and enter a phase of equilibrium.
When a tumor remains quiescent in the equilibrium phase but still cannot be completely eliminated by the immune system, some tumor cells may enter the escape phase and gain an advantage over the immune system, leading to the resumption of tumor growth.
The mechanism by which tumors evade the immune system
CD8+ cytotoxic T cells are an important component of anti-tumor immunity. There are many ways for tumor cells to reduce their likelihood of being recognized, such as reducing MHC I expression.
When tumor cells lose MHC I expression, this triggers a natural killer cell response.
In addition, tumor cells can also inhibit the activity of T lymphocytes by expressing immune checkpoint molecules such as PD-L1 or FasL, preventing their attack and creating an immunosuppressive environment conducive to tumor growth.
The influence of tumor microenvironment
The tumor microenvironment contains various immune cells and the cytokines they secrete, which work together to form an environment that promotes tumor growth. For example, tumor cells and exogenous cells such as critical monocytes secrete TGF-β, which further transforms CD4+ T cells into regulatory T cells (Treg). This transformation can cause immune suppression in tumors.
Tumor-associated macrophages mainly have an alternatively activated M2 phenotype, and they play an important role in promoting tumor growth and angiogenesis.
Understanding the interactions of these microenvironments is critical to developing effective treatments.
Exploration of immunomodulatory methods
Faced with tumor cells' evasion of the immune system, scientists are exploring various immune regulation methods. Monoclonal antibodies, such as anti-CTLA4 and anti-PD-1, are the focus of current research. These molecules enhance immune responses by inhibiting inhibitory signals, such as ipilimumab and nivolumab.
CAR-T cell technology using genetic engineering is gradually being pushed into clinical application, bringing new hope to tumor immunotherapy.
The development of cancer vaccines is also an effective way to use tumor antigens to activate the immune system.
The relationship between chemotherapy and immunity
Recent studies have shown that chemotherapy can promote immune responses to chemotherapy-resistant tumor cells through programmed cell death. Past research has suggested that necrotic cell death can stimulate an immune response, while apoptosis may rarely trigger such a response.
Research shows that some anti-tumor agents can create a favorable immune environment and initiate T cell activation when killing cancer cells.
However, in the face of highly immunosuppressed advanced cancer patients, how to effectively activate their T cells is still a big challenge, which requires more in-depth exploration.
The proposal of cancer immune surveillance not only re-understands the function of the immune system, but also brings unprecedented opportunities for cancer treatment. As medicine advances, will there be more breakthroughs in the future to combat this deadly disease?
