Characteristics of Tumor Antigens
Malignant neoplasms possess extremely low immunogenicity. This means that the antigenic profile of transformed cells has only minor differences from normal body cells, significantly hindering their timely recognition by the immune system.
There are several main types of tumor-associated antigens that can serve as targets for defense reactions:
- Oncofetal antigens.
- Products of various oncogenes.
- Specific viral antigens (in virus-induced tumors).
- Normal cellular proteins that are overexpressed.
How Antitumor Defense Works
Cell-mediated immunity plays the absolute leading role in destroying transformed tissues. The main effector cells here include activated macrophages, cytotoxic T lymphocytes (CTLs), as well as NK cells (natural killers) and NKT cells.
The process of cytotoxic response activation and threat elimination consists of several sequential steps:
- Recognition: Antigen-presenting cells (primarily macrophages and dendritic cells) capture and recognize the tumor antigen.
- Presentation: The processed antigen is presented 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 into fully functional immune cytotoxic CD8+ T lymphocytes, ready for attack.
- Destruction: Ready effectors locate the target cell and destroy it.
Mechanisms of Tumor Immunosuppression
A tumor does not merely hide passively; it creates a specific microenvironment around itself that actively suppresses immune responses through cellular and humoral factors.
Cellular suppression factors:
- Type 2 T helpers ($T_H2$): Their activation is promoted by antigen-presenting cells already associated with the tumor.
- Regulatory T cells ($T_{Reg}$): A sharp increase in their number and activity is noted among tumor-infiltrating lymphocytes (TILs).
- 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-$eta$) and interleukin-10 (IL-10).
The role of humoral immunity: Although B lymphocyte activity is often elevated, the protective function of the humoral response in oncogenesis is highly questionable. In practice, the blocking effect occurs: produced antibodies bind to surface antigens of the tumor without killing it. Instead, they "shield" the cancer cells, physically preventing the cytopathogenic action of more efficient cell-mediated immunity.
The Tumor "Escape" Phenomenon
In some cases, the immune response proves ineffective, allowing the malignancy to survive and progress. This phenomenon is known as the "escape" phenomenon. It is driven 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 stimulatory signals.
Second, there is downregulation of MHC (major histocompatibility complex) expression. A reduction in the number of these crucial molecules on the membrane of cancer cells causes the immune system (especially the T-cell arm) to physically lose the ability to recognize them as foreign and dangerous.