Macrophages are found in all tissues and show great functional diversity, including the recognition and clearance of foreign, aged, and damaged cells. Activated macrophages can be used effectively as a cancer immunotherapy; they can kill cancer cells by themselves in a direct manner or indirectly through recruitment of other immune cells, such as cytotoxic T-lymphocytes.
Mechanisms of macrophage cancer therapy
The mechanisms by which macrophages can recognize and kill cancer cells is multiple-sided:
1. Direct killing through the release of harmful products (such as oxygen radicals).
The direct cytotoxic function of macrophages requires activation either with bacterial cell wall products or with various cytokines. Upon activation, the macrophages either secrete several substances that are directly involved in tumor cell killing i.e. tumor necrosis factor (TNF) and nitric oxide (NO), or they actively take up the cancer cells by phagocytosis.
2. Direct cytolysis of cancer cells through antibody-dependent cellular cytotoxicity.
This form of cell lysis involves the recognition and binding of an antibody-coated cancer cell by the macrophage. After binding, cancer cells will be killed by the release of cytotoxic mediators or phagocytosis.
- Macrophage-mediated cancer immunotherapy is a slow, cell-to-cell contact-dependent process requiring 1–3 days. The susceptibility of the cancer cells to be directly killed by the macrophages varies greatly due to heterogeneity within cancers.
3. Indirect killing by recruitment of other immune cells that can lyse the cancer cells.