A major function of the immune system is to recognize foreign objects (viruses, bacteria, parasites, splinters, and anything else that isn’t supposed to be in your body) and destroy them. Immune cells do this by recognizing specific targets on the surface of the item to be destroyed. Cancer cells are abnormal and may be recognized as ‘foreign’ by immune cells. Immune cells recognize small molecular ‘flags’ associated with tumor cells (called tumor specific antigens (TSAs) or tumor associated antigens (TAAs)). Immune cells can then kill these cancer cells.
Note: An antigen can be defined as anything the immune system can recognize. It is a general term. Antigens can be proteins, sugars, lipids, nucleic acids, or hybrid molecules. Most antigens are proteins.
If the immune system is able to recognize and kill cancer cells, why do people get cancer?
It is thought that most cancers are caught very early and eliminated by the immune system. The cancers that survive have to be able to evade the immune system. It turns out that there are several ways that cancer cells avoid being recognized and killed. These include:
- Cancer cells form from normal cells. Because cancer arises from a person’s own cells, it’s trickier for the immune system to recognize cancer cells than to identify a truly foreign invader like a virus.
- Cancer cells with the most targets on them are most easily killed by the immune system. This sounds like a good thing, and it can make tumors shrink, but after a while, the cancer cells that are left have less targets on their surface. Those with the least amount of target antigens on their surface have the best chance of surviving, and tend to take over, making the cancer resistant to immune cells. It is similar to treating a lawn with weed killer. Any weeds that are resistant will survive and grow. After that, the weed killer will not work anymore. The immune system accidentally ‘selects’ for cancer cells that it can’t recognize.
- Cancer cells can hijack normal control systems to turn the immune system ‘off’ in and around the tumor. To keep the immune system under control, there are several controls (like ‘on-off’ switches) that work to regulate the activity of immune cells. Some cancer cells are able to flip that switch, turning the immune system off in the area around and in the tumor. Treatments designed to reverse this are very promising and are described more below.
- Cancer cells can evade the immune system by making less of the ‘self’ signals that immune cells use to recognize defective or infected cells.Cancer proteins can be shown to the immune system by being stuck to cellular versions of flagpoles. By taking down the poles, cancer cells prevent this from happening and are able to avoid being recognized and killed.
- Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara HM, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Choi BK, Kwon BS. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015 Mar 25. pii: S1044-579X(15)00019-X [Epub ahead of print] [PUBMED]
- Seliger B. Strategies of tumor immune evasion. BioDrugs. 2005;19(6):347-54. [PUBMED]
- Poggi A, Musso A, Dapino I, Zocchi MR. Mechanisms of tumor escape from immune system: role of mesenchymal stromal cells. Immunol Lett. 2014 May-Jun;159(1-2):55-72. Epub 2014 Mar 20. [PUBMED]