Non-immune (nonspecific) mechanisms
They provide baseline surveillance to maintain normal cellular composition. Innate immunity relies on cellular factors (phagocytes, dendritic cells, Kupffer cells, NK cells, astrocytes) and humoral substances:
- TNF-α (tumor necrosis factor alpha): Triggers the apoptosis program in blast cells, stimulates the production of reactive oxygen species (ROS) by macrophages, and induces thrombus formation in tumor microvessels, causing ischemia and necrosis.
- Contact and allogeneic inhibition factors: Suppress invasion and proliferation, and disrupt the metabolism of isolated tumor cells.
- α-Lipoproteins (α-LP): Exert a direct cancerolytic effect on tumor cells without damaging healthy tissues.
Specific immune mechanisms
A key role in targeted anti-blastomate resistance is played by factors reacting to specific tumor antigens (Ag):
- Specific cytotoxic T lymphocytes: They destroy target cells either through direct contact or from a distance by releasing cytotoxic agents into body fluids.
- Specific immunoglobulins (Ig): Synthesized by plasma cells. They work remarkably well against individual blast cells (e.g., in hemoblastoses), but are practically useless against a formed tumor node, since antigens within it are largely inaccessible to antibodies.
Why does the defense fail?
Carcinogens themselves are capable of suppressing the activity of defense factors. In addition, tumor cells actively defend themselves by inducing the development of pathological tolerance. The main reasons for the inefficiency of immunity:
- Shielding: Blast cells become coated with fibrin or ineffective antibodies, hiding their antigenic determinants.
- Receptor blockade: Free antigens shed from the tumor bind killer cell receptors in vain.
- Camouflage as "self": Expression of embryonic proteins to which the body has physiological tolerance.
- Profile alteration (Antigenic drift): Due to the high mutation rate, cells constantly change their antigens.
- Suppression of APCs: The tumor microenvironment secretes IL-10 and endothelial growth factor. This impairs antigen processing and presentation to CD4+ and CD8+ lymphocytes.
Negative checkpoints
Normally, immune checkpoints are necessary to prevent reactions against self-tissues. The tumor modifies healthy cells and co-opts these systems to survive:
- CTLA-4 (CD152): Inhibits T-cell activation and IL-2 secretion. This receptor binds to the costimulatory molecule B7 with a higher affinity than the stimulatory receptor CD28.
- PD-1: Programmed cell death protein. By interacting with its ligands PD-L, it suppresses immune cell activity, allowing the neoplasm to evade attack.
Briefly: answers to topical questions
What mechanisms do cytotoxic T-lymphocytes use to destroy a tumor cell?
Specific cytotoxic T-lymphocytes have a dual mechanism of action for tumor cell destruction.
- Direct contact with the tumor cell.
- Indirectly (at a distance): release of cytotoxic agents into biological fluids.
Furthermore, their mechanism is analogous to secretory (perforin-granzyme) lysis, in which cytotoxic proteins (perforins and granzymes) are released into the contact zone with the target cell, leading to DNA fragmentation, disruption of membrane integrity, and cell death via apoptosis and necrosis.
Which immunoglobulin classes are most effective in the humoral antitumor response?
The humoral immune response to tumor antigens is formed, but lacks a protective character. It is ineffective due to the destruction of complement system components by factors on the cell surface and weak Fc-dependent macrophage recruitment. Moreover, the "tumor enhancement effect" phenomenon exists, wherein antibodies block target antigens, protecting the tumor cell from destruction. Specific immunoglobulin classes effective for tumor defense are not named in the sources.
To remember the reasons for antibody inefficiency, imagine a tumor node as a fortress: immunoglobulins are great at catching "lone scouts" (isolated blast cells in the blood), but cannot breach the "walls" (inaccessibility of antigens inside the node).
Class and exam questions
How does tumor necrosis factor alpha (TNF-α) kill cancer cells?
It acts comprehensively: triggers apoptosis, enhances ROS production by phagocytes, and causes microvascular thrombosis of the tumor, leading to its ischemia and necrosis.
Why do specific antibodies not always cope with a tumor?
They are highly effective against single cells (e.g., in hemoblastoses), but antigens inside a dense tumor node are practically inaccessible to them.
What is antigenic drift in oncology?
This is the process of altering the antigenic profile of a tumor cell due to constant gene mutations, allowing it to "escape" the specific immune response.
What else to study on this topic
- The role of dendritic cells and Kupffer cells in non-immune antitumor surveillance
- Mechanisms of allogeneic and contact inhibition of tumor cells
- The effect of endothelial growth factor and IL-10 on antigen-presenting cells
- Molecular interaction of the CTLA-4 receptor with the costimulatory molecule B7
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