Characteristics of tumor antigens
Malignant neoplasms have extremely low immunogenicity. This means that the antigenic profile of transformed cells differs only slightly from normal body cells, which significantly complicates their timely recognition by the immune system.
There are several main types of tumor-associated antigens that can become targets for defense reactions:
- Carcinoembryonic antigens.
- Products of various oncogene activities.
- Specific viral antigens (in the case of virus-induced tumors).
- Normal cellular proteins that are in a state of overexpression.
How antitumor defense works
Cellular immunity plays an absolutely leading role in the destruction of transformed tissues. The main effector cells here are activated macrophages, cytotoxic T lymphocytes (CTLs), as well as NK cells (natural killers) and NKT cells.
The process of cytotoxic response activation and threat destruction consists of several consecutive stages:
- Recognition. Antigen-presenting cells (primarily macrophages and dendritic cells) capture and recognize the tumor antigen.
- Presentation. The processed antigen is displayed to naive CD8+ T lymphocytes. This can occur directly or with the support of type 1 T helper cells ($T_H1$).
- Differentiation. Naive T cells mature, turning into fully-fledged immune cytotoxic CD8+ T lymphocytes ready for attack.
- Destruction. Ready effectors find the target cell and destroy it.
Mechanisms of tumor immunosuppression
The tumor does not just passively hide; it forms a specific microenvironment around itself that actively suppresses immune reactions using cellular and humoral factors.
Cellular suppression factors:
- Type 2 T helper cells ($T_H2$): Their activation is provoked by antigen-presenting cells that are already associated with the tumor.
- Regulatory T lymphocytes ($T_{Reg}$): There is a sharp increase in their number and activity among tumor-infiltrating lymphocytes (TILs — tumor-infiltrating lymphocytes).
- Myeloid-derived suppressor cells.
Cytokine suppression: The tumor microenvironment actively produces cytokines with pronounced immunosuppressive effects. Key among them are transforming growth factor-$\beta$ (TGF-$\beta$) and interleukin-10 (IL-10).
The role of humoral immunity: Although a predominance of B lymphocyte activity is often observed, the protective function of the humoral response in oncogenesis is highly questionable. In practice, the shielding effect is realized: the produced antibodies bind to surface antigens of the tumor, but do not kill it. Instead, they "cover" the cancer cells, physically preventing the cytopathogenic action of the more effective cellular immunity.
Tumor "escape" phenomenon
In a number of cases, the immune response proves ineffective, allowing the malignancy to survive and progress. This phenomenon is termed the "escape" phenomenon. It is caused by several critical failures.
First, there is a deficiency of important cytokines. Insufficient production levels of tumor necrosis factor (TNF), interferons, and interleukin-2 (IL-2) deprive the immune system of necessary stimulating signals.
Second, there is a decrease in MHC expression (major histocompatibility complex). A reduction in the number of these crucial molecules on the membrane of cancer cells leads to the immune system (especially the T-cell link) physically losing the ability to recognize them as foreign and dangerous.
Briefly: answers to topical questions
Which marker receptors and molecules on the surface of tumor cells undergo decreased expression to escape the T-cell link?
To escape recognition by the T-cell link of immunity, the expression of major histocompatibility complex molecules decreases on the surface of tumor cells. This phenomenon is one of the reasons for the inefficiency of the immune response, allowing the tumor to survive.
- Major histocompatibility complex molecules (MHC) — a decrease in their number on the membrane of cancer cells makes their recognition by the immune system impossible.
Class and exam questions
Why don't antibodies destroy the tumor?
Instead of destruction, antibodies often cause a "shielding effect." They bind to antigens on the surface of the neoplasm, thereby hiding the target from the destructive action of T lymphocytes and macrophages.
Which cells are the main tumor killers?
The main cytopathogenic role is played by effectors of cellular immunity: activated macrophages, cytotoxic CD8+ T lymphocytes (CTLs), as well as NK and NKT cells.
Why does a tumor need to reduce the number of MHC molecules on its membrane?
MHC molecules are necessary for antigen presentation to T lymphocytes. By reducing their number, the cancer cell becomes "invisible" to the immune system, which is the basis of the "escape" phenomenon.
What else to study on this topic
- Features of tumor antigen presentation by dendritic cells
- The role of type 1 and type 2 T helper cells in the polarization of the antitumor response
- Mechanisms of action of regulatory T lymphocytes (Tregs) in the tumor microenvironment
- Immunosuppressive properties of TGF-$\beta$ and IL-10 cytokines
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