Cancer immune evasion describes the collection of strategies that cancerous cells use to avoid being identified and eliminated by the body’s immune system. This capability is a significant factor in how cancers develop, grow, and spread. When the immune system is unable to perform its protective functions, malignant cells can proliferate without interference. Understanding how tumors manage to escape this surveillance is a central focus of cancer research, as it directly informs the development of new and more effective treatments.
The Immune System’s Anti-Cancer Role
The immune system is constantly engaged in a process known as immunosurveillance, a patrol throughout the body to find and destroy abnormal cells. This function is a primary defense against the development of cancer. This protective process relies on the ability of the immune system to distinguish healthy “self” cells from potentially harmful “non-self” or altered cells.
Lymphocytes, particularly T cells and natural killer (NK) cells, are central to this defense. T cells identify specific markers on the surface of cancer cells, called tumor antigens, which signal that the cell is abnormal. Once a T cell recognizes an antigen, it can directly kill the cancerous cell or coordinate a broader immune attack. NK cells provide a more immediate response, able to destroy abnormal cells that have lost the typical surface markers that identify them as healthy. This constant monitoring and response system is designed to eliminate cancerous cells before they can form a detectable tumor.
Strategies Cancer Cells Use to Evade Immune Attack
Cancer cells develop specific methods to avoid being detected and destroyed by the immune system.
- Hiding from T cells by reducing the number of Major Histocompatibility Complex (MHC) class I molecules on their surface. These molecules normally display tumor antigens, and with fewer of them, the cancer cell becomes effectively invisible.
- Exploiting immune checkpoints, which are pathways the immune system uses to regulate its own activity. Cancer cells can express proteins, such as Programmed Death-Ligand 1 (PD-L1), which binds to the PD-1 receptor on a T cell and sends a “stop” signal that deactivates it.
- Creating an immunosuppressive environment by releasing substances like transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10). These cytokines inhibit the activity of aggressive immune cells and can attract other cells that further dampen the anti-tumor response.
- Resisting the killing mechanisms of immune cells. Cytotoxic T cells and NK cells induce programmed cell death (apoptosis) in their targets, but some cancer cells acquire mutations that make them resistant to these signals, allowing them to survive an attack.
The Tumor Microenvironment’s Role in Immune Evasion
The area immediately surrounding a tumor, known as the tumor microenvironment (TME), actively helps protect it from the immune system. The physical structure of the tumor can form a barrier that prevents immune cells from penetrating it. This dense network of cells and structural proteins can effectively wall off the cancer from patrolling lymphocytes.
The TME is often populated by cells that actively suppress anti-tumor immunity. Cancer cells release signals that recruit cell types like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). These cells specialize in shutting down immune responses, neutralizing the efforts of any cancer-fighting T cells that manage to infiltrate the tumor.
Metabolic conditions within the TME also contribute to immune evasion. Tumors consume large amounts of nutrients, creating an environment low in oxygen and essential resources like glucose. These harsh conditions impair the function of anti-tumor immune cells, which have high energy demands. This altered chemical landscape protects the tumor and can promote processes that support its growth and expansion.
Consequences and Clinical Implications of Immune Evasion
When cancer cells successfully evade the immune system, they are free to grow, leading to tumor progression and invasion of surrounding tissues. Immune evasion is also a facilitator of metastasis, the process by which cancer spreads to distant parts of the body. Cells that can avoid immune detection are more likely to survive and establish new tumors in other organs.
A tumor’s ability to suppress the immune system can also contribute to resistance against other cancer treatments. Therapies like chemotherapy and radiation work by damaging cancer cells, and an active immune system helps clear away these damaged cells. If the immune system is suppressed, it may not effectively assist in this cleanup, allowing some damaged cancer cells to survive.
A deeper understanding of these evasion mechanisms has driven the development of modern immunotherapy. Treatments like immune checkpoint inhibitors are designed to block the “stop” signals, such as PD-1/PD-L1, that cancer cells use to deactivate T cells. By inhibiting these checkpoints, these drugs “release the brakes” on the immune system, allowing it to recognize and attack cancer cells.