I read a paper describing the interplay between two proteins, CD47 and cell-surface calreticulin (CRT), on the surface of cancer cells (link). The paper makes a number of fascinating points.
Obviously, it is in the body's overall best interest to destroy any cancer cells. Such cells can be seen as foreign invaders attacking the body. Typically, when the body is under such microbial attack, there is a response from the immune system. The immune system is able to detect that there is an attack, and to specifically identify what the attackers are. Once identified they are tagged with antibodies, and can then be engulfed by white blood cells, eventually to be destroyed.
Such is the case for a normal attack. However, this is often not seen in cancer. Frequently, the body does not recognize that cells are cancerous. Considering that such cells come from the same body, and may have previously been functioning properly, this isn't completely surprising. However, cancer cells just plain don't behave like normal cells anymore. They forcefully break away from other cells, they absorb vast quantities of nutrients, and they proliferate without control. Even so, the immune system fails to detect them. Of course, if the immune system doesn't see them, then as far as it knows there is no problem.
From the point of a bunch of cancer cells, it is in their best interest to avoid the immune system. They no longer work for the body, but they happily take up shelter and food within. If their numbers are not being reduced by the immune system, then they can grow that much more quickly. In other words, it is no random fluke that the immune system is blind to them: mutations that favor becoming covert to the immune system are both favorable and likely.
The authors of the paper investigated this phenomenon in detail. It has been previously known that cancer cells often have large amounts of CRT on them. CRT is a signal to the immune system. Phagocytes, which engulf and destroy invaders, are attracted to CRT. So something carrying large amounts of CRT is essentially screaming to be eaten by the immune system. However, this seems contradictory, given that cancer typically avoids the immune system.
The reason for this was large volumes of CD47, expressed in tandem with CRT. CD47 is sort of the counter-CRT. Phagocytes avoid things covered with CD47, making it essentially a "don't eat me" signal. The authors performed a significant amount of experimentation proving that it was, in fact, the CD47 that was preventing the cancer cells from being engulfed.
There are a number of follow-up questions to this. First and foremost, why don't cancer cells simply not produce CRT? The default of a healthy immune system is not to eat something, so without the CRT signal it probably wouldn't attack. Instead, cancer cells go through the trouble of producing both CRT and CD47. Personally, I think this suggests that CRT evolved much earlier than CD47, and it has been tied into a variety of core metabolic pathways. The paper mentions that stressed or damaged cells generally give off CRT, and the bizarre behavior of cancer cells constantly puts them under high stress. CRT is probably produced by some necessary pathway under stressful conditions. The cancer cell needs the pathway, and it can't avoid the stress, so something else must be done. It can't intelligently say "turn off CRT production", so the quick mutational fix is to overproduce CD47.
There is a second important question. If cancer cells have CD47, then is a possible course of treatment to selectively destroy or disable CD47 and allow the immune system to do its job? The paper mentions this possibility, pointing out that most (but not all) tissue types do not typically have CD47. Such tissues should be theoretically unaffected by a treatment that affects only CD47, though one can never know for sure without actual clinical trials. Personally, I think there is some promise in this, though there still needs to be a significant amount of research performed before an anti-CD47 cancer treatment is developed.
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