Cancer and autoimmune diseases

[docnet]

TL;DR Summary

Dawkins proposes autoimmune diseases could be the result of an evolutionary arms race between cancer and the immune system.

Richard Dawkins, a famous evolutionary biologist, thinks there is an evolutionary connection between cancer and the immune system. To paraphrase his work, autoimmune diseases are the result of the evolutionary arms race between the body and cancer cells. I'm not an immunologist nor a cancer biologist, but I've recently taken graduate level courses in the two subjects. There is a real evolutionary arms race between cancer and the immune system. The immune system has been evolving to recognize cancer cells that are constantly finding novel ways to evade being killed. There is a lot of research in the field of cancer biology and it can be quite a fascinating read. But, I don't know why Dawkins thinks autoimmune disease are caused by cancer and the immune system. Just curious if anyone has an idea?

 

[BillTre]

I would not say an evolutionary arms race between cancer and immune system cells.
This implies that the cancer cells have some kind of evolutionary benefit from being cancerous. With very few exceptions (Tasmanian Devil face cancer and a dog reproductive tract cancer) the cencer cells die when their host organism dies. They therefore generate no evolutionary lineage and no progeny. They themselves are not evolving.

The bodies of the more complex metazoan animals are generated by and kept under proper control by extremely complex developmental controls.
For various reasons these controls can malfunction and cells are not under their normal growth and movement controls. This results in rebellious growths of cancerous cells that take away from the body's reserves and functionality, and spread throughout the body.

One function of the immune system is to provide a response system for these developmental problems by identifying cancerous cells and eliminating them (through mechanisms of molecular recognition of moelcules on the surfaces of cancerous cells.
This mechanism itself can malfunction and direct an immune attack against particular cells of the body, which is what an autoimmune disease does.

 

[docnet]

This implies that the cancer cells have some kind of evolutionary benefit from being cancerous. With very few exceptions (Tasmanian Devil face cancer and a dog reproductive tract cancer) the cencer cells die when their host organism dies.

Yes, that's what I was thinking as well. The term evolution by natural selection should not be used to describe cancer cells. Richard Dawkins describes evolution by natural selection with respect to individual genes, instead of whole organisms. His version of evolution is not compatible with cancer genes because many cancer genes spontaneously arise by mutation and survive only as long as the lifespan of the host. Neither Dawkin's Selfish Gene nor Darwin's idea of evolution on the individual scale applies to spontaneously arising and heritable cancer genes.

The cancer research scientist who came to give half of the lectures sometimes used the term evolution to describe the process of changing cancer cells. But I don't think she meant it in the frame that most are familiar with. The cancer cells change to avoid being detected, engaged, and killed by immune cells. For example, cancer cells change their immunogenic markers into non-immunogenic markers, and start secreting immunogenic free ligands that bind receptors of natural killer cells. Whenever researchers come across new types of cancer cells, they conduct research to develop novel drugs and new methods of treatment to kill the cancer cells.

There is a lot of literature written on cancer immunology. I think my professor mentioned an entire textbook written about the disregulation of P53 in cancer cells, but I didn't read it. The same probably goes for autoimmune diseases. And I am not an expert in either subject.

 

[atyy]

The cancer cells change to avoid being detected, engaged, and killed by immune cells. For example, cancer cells change their immunogenic markers into non-immunogenic markers, and start secreting immunogenic free ligands that bind receptors of natural killer cells. Whenever researchers come across new types of cancer cells, they conduct research to develop novel drugs and new methods of treatment to kill the cancer cells.

Remarkably, it is now sometimes possible to disable the defences of cancer cell, so that immune cells can kill the cancers more effectively.
https://en.wikipedia.org/wiki/PD-1_and_PD-L1_inhibitors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883082/

A second approach adds something to immune cells to enable them to attack cancers.
https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell
https://www.bbc.com/news/uk-england-hereford-worcester-51147653

 

[docnet]

Remarkably, it is now sometimes possible to disable the defences of cancer cell, so that immune cells can kill the cancers more effectively.

Yes, PD-1 is a protein receptor on certain types of white blood cells that's naturally present as a means to down-regulate the T cell activity by healthy cells. Cancer cells that display PD-L1 (L for ligand) survive by deactivating the T cells and preventing the T cells from killing them. The PD-L1 inhibitors are drugs designed to bind to the cancer cells as the name suggests and prevent T cell deactivation. CTLA-4 works by a similar mechanism. (I had to look it up to refresh my memory).

A second approach adds something to immune cells to enable them to attack cancers.

The chimera is circular piece of DNA which is synthesized in the lab specifically for insertion into white blood cells that have been isolated from the patient. The chimeric DNA codes for a version of the T cell receptor which recognizes specific markers of the cancer the patient is suffering from. The DNA is transcribed and translated by the cell's machinery and produces T cell receptors that will recognize and kill the cancer cells. The T cells are then provided with specific molecular signals to proliferate and become activated. They are then injected back into the patient for immunotherapy. It's fascinating how the new T cell receptors are simply produced from the linear programming of DNA. I'm happy to say I still kind of remember learning this last year.

 

[BillTre]

The cancer cells change to avoid being detected, engaged, and killed by immune cells. For example, cancer cells change their immunogenic markers into non-immunogenic markers, and start secreting immunogenic free ligands that bind receptors of natural killer cells.

Over the span of the host organism, there will be selection among the cancer cells within a given organism for those that best evade the host's defenses. So, in that sense there is selection, ut all that ends with the life of the host, unless the cancer ca invade new hosts, like the Tasmanian Devil face cancer or the dog reproductive tract cancer. Those are cancer cell that are evolving over longer periods of time.

Perhaps Dawson was referring to the differing selective forces on the immune system to eliminate cancer cells and not attack one's own normal cells.

 

[docnet]

Over the span of the host organism, there will be selection among the cancer cells within a given organism for those that best evade the host's defenses.

Yes, this is how it works. Every single day many spontaneously arising cancer cells are killed by the immune system of a perfectly healthy, normal, young person. The estimated figure is several orders of magnitude greater than 1000 cells per day, I can't remember the exact number but it's a huge number. The reality is that cancer cells arise in our bodies all the time, we just don't notice them. Because, they are found and killed by the immune system before they grow into tumors. A cancer cell can arise with a mutation that allows it to evade the immune system, which then grows into a malignant tumor and requires a carefully planned medical intervention to kill the specific types cancer cells in that individual.

Cancer cannot evolve in the same way that bacteria evolved into multicellular organisms, or how wolves evolved into dogs. In order for it to evolve by Darwinian evolution, its effect in the individual must increase the chances of its survival. A heritable gene for cancer does not affect the phenotype of the individual in any way that favors the chances of the individual having more offspring. In the case of the transmissible non-human cancers you described, yes, these cancer cells evolve in principle in the same way viruses do; by picking up mutations over time that favors its chances of transmission from host to host.

Perhaps Dawson was referring to the differing selective forces on the immune system to eliminate cancer cells and not attack one's own normal cells.

I don't think we should automatically assume that Dawkins is an expert in the area of molecular immunology, which is a rigorous field of biology different from evolutionary biology. From what we were taught last year, the human immune system has redundancies that evolved over time to ensure it does not attack self tissue. For example, negative selection of T cells during their normal development in the thymus selects for T cells that don't recognize self peptides. In the cases of autoimmune diseases, there is evidence affected individuals carry alleles that make their immune systems susceptible recognizing a specific self peptide as foreign. The adaptive immune system is alerted against, for example, the cells in the pancreas in the case of type 1 diabetes. The recognition of self peptide as foreign triggers a life long autoimmune response that is difficult to treat in principle.

 

[jim mcnamara]

Can you post a good primary source for us to read? Thanks

 

[atyy]

BTW, did Dawkins really propose a link between cancer and the evolution of autoimmune diseases? I did a quick google but didn't find any reference for such a proposal.

 

[BillTre]

References:

evolution of cancer cells
immune response to cancer
immune system

 

[docnet]

Can you post a good primary source for us to read? Thanks

here is the PDF file of the textbook we used in cellular& molecular immunology class (the download link is not my own). I think the textbook is a great source for introductory immunology. I tried to post the relevant chapter of The Biology of Cancer by Weinberg here, but the file is too large. There is around 70 pages of relevant information on cancer immunology and immunotherapy. I will try to send it by PM if you are still interested in it.

BTW, did Dawkins really propose a link between cancer and the evolution of autoimmune diseases? I did a quick google but didn't find any reference for such a proposal.

I think he speculated on the idea during a public lecture and it was not a formal proposition.

 

[Laroxe]

I'm surprised at Dawkins, cancer is overwhelmingly a disease of old age in humans & therefore unlikely to occur during most peoples reproductive period. Any changes that occur when reproduction has finished will have no impact on future generations. There are plenty of things which can have a role in cancer genesis, these can include bacteria, virus's, fungi and a whole range of other biological toxins.
While few cancers are likely to be heritable there are probably a huge number of heritable differences in people that might influence their risk and the cells that make up a cancer are subject to selection as they develop more differences. So in the cancer cell population we can expect there to be a distribution of abilities within the cell lines, there are also significant physical differences so tumours have cell populations that are dead, anoxic, senescent and actively multiplying some cells may become mobile, pushing into other tissues (invasive) or entering the bloodstream (metastatic). These might all effect the way in which our immune system can identify and attack cancers. All of our cells have ways to protect themselves from our immune system which when activated becomes increasingly aggressive causing lots of collateral damage, some cancer cells are particularly good at supressing immune cells, its really just a variation on a normal ability. Many may have variations on the receptor sites they express others develop strategies to resist apoptosis.
There isn't really a single way to understand autoimmunity other than the fact it reflects the way our immune system works, understanding why some of the errors occur can be difficult. Women, because they can have babies have a number of differences in the way their immune system works and it can in fact be even more aggressive. This also means women become more prone to autoimmune conditions as they get older.