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Antitumor Immunity

For medical students2 min readUpdated 2026-10-10

Antitumor immunity is a complex of cellular mechanisms aimed at detecting, arresting the growth of, and destroying cells with a malignant genotype and phenotype. This defense system is triggered when antimutational barriers fail and oncogenes are activated.

Main GoalDestruction of genotypically and phenotypically foreign cells or suppression of their growth.

Blood MarkerA decrease in serum α-lipoprotein levels indicates the presence of a neoplasm.

Immune EvasionThe tumor constantly changes its antigens (*antigenic drift*) and hides under a layer of fibrin.

CheckpointsCTLA-4 and PD-1 receptors are exploited by tumor tissue to suppress T cells.

Non-Immune (Nonspecific) Mechanisms

These mechanisms perform 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 apoptosis in blast cells, stimulates the production of reactive oxygen species (ROS) by macrophages, and induces thrombosis in tumor microvessels, leading to ischemia and necrosis.
Factors of contact and allogeneic inhibition: Suppress invasion, proliferation, and disrupt the metabolism of isolated tumor cells.
α-Lipoproteins (α-LPs): Exert a direct cancerolytic effect on tumor cells without damaging healthy tissues.

Specific Immune Mechanisms

Factors that react to specific tumor antigens (Ags) play a key role in targeted anti-blastomatous resistance:

Specific cytotoxic T lymphocytes: Destroy target cells either through direct contact or distantly by releasing cytotoxic agents into biological fluids.
Specific immunoglobulins (Igs): Synthesized by plasma cells. They work exceptionally well against isolated blast cells (e.g., in hemoblastosis), but are practically ineffective against a formed tumor mass because internal antigens are largely inaccessible to antibodies.

Why the Defense Fails

Carcinogens themselves can suppress defense mechanisms. Furthermore, tumor cells actively protect themselves by inducing pathological tolerance. The main causes of immune failure include:

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 (decoy effect).
Mimicking "self": Expression of embryonic proteins to which the organism has physiological tolerance.
Profile alteration (antigenic drift): Due to a high mutation rate, cells constantly change their surface antigens.
Suppression of APCs: The tumor microenvironment secretes IL-10 and vascular endothelial growth factor (VEGF). This impairs antigen processing and presentation to CD4+ and CD8+ lymphocytes.

Negative Checkpoints

Normally, immune checkpoints are necessary to prevent reactions against self-tissues. Tumors modify healthy cells and hijack 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 1. By interacting with its ligands (PD-L), it suppresses immune cell activity, allowing the neoplasm to evade attacks.

Mnemonic

To remember the reasons for antibody ineffectiveness, picture a tumor mass as a fortress: immunoglobulins easily catch "lone scouts" (isolated blast cells in the blood), but cannot break through the "walls" (inaccessibility of antigens inside the solid tumor mass).

Frequently asked questions

What mechanisms do cytotoxic T lymphocytes use to destroy a tumor cell?

Cytotoxic T lymphocytes utilize a dual mechanism of action to destroy tumor cells:

Direct contact with the tumor cell.
Indirectly (distantly): release of cytotoxic agents into biological fluids.

Additionally, their mechanism resembles secretory lysis (perforin-granzyme pathway), in which cytotoxic proteins (perforins and granzymes) are released into the contact zone with the target cell, leading to DNA fragmentation, membrane integrity disruption, and cell death via apoptosis and necrosis.

Which immunoglobulin classes are most effective in the humoral antitumor response?

A humoral immune response to tumor antigens does occur, but it 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. Furthermore, the phenomenon of "tumor enhancement effect" exists, where antibodies block target antigens, protecting the tumor cell from destruction. Specific immunoglobulin classes effective for tumor defense are not explicitly named in the sources.

How does tumor necrosis factor (TNF-α) kill cancer cells?

It acts comprehensively: it triggers apoptosis, enhances ROS production by phagocytes, and induces microvascular thrombosis within the tumor, leading to ischemia and necrosis.

Why don't specific antibodies always cope with tumors?

They are highly effective against single cells (e.g., in leukemias/lymphomas), but antigens inside a dense tumor mass are practically inaccessible to them.

What is antigenic drift in oncology?

It is the process of altering the antigenic profile of tumor cells due to continuous gene mutations, allowing them to "escape" the specific immune response.

Go deeper

The role of dendritic cells and Kupffer cells in non-immune tumor surveillance
Mechanisms of allogeneic and contact inhibition of tumor cells
Impact of vascular endothelial growth factor and IL-10 on antigen-presenting cells
Molecular interaction of the CTLA-4 receptor with the costimulatory molecule B7