If a cancerous tumor has a lot of mutations in them why can't the immune system detect them? If a person has cancer could this somehow alter the person's immune system so it doesn't function effectively to detect greatly mutated cells? Does the fact that a tumor is 'made' of 'mutated' non-foreign human cells help it to be undetectable?
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1$\begingroup$ "Does the fact that a tumor is 'made' of 'mutated' non-foreign human cells help it to be undetectable?" This is pretty much it. The more mutations a cancer has, the more likely your immune system will respond. I saw a talk by Steven Rosenburg about cancer immunotherapy, might be interesting for you. $\endgroup$– user137Commented Aug 15, 2015 at 12:26
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$\begingroup$ This is a good question and I have upvoted already, but you could consider adding some more information from your own background research (e.g. on minimum and typical numbers of mutations occurring in cancers) to make it more helpful to future readers. $\endgroup$– arboviralCommented Feb 11, 2018 at 19:19
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$\begingroup$ Have you done any research at all into how the immune system works? $\endgroup$– swbarnes2Commented Oct 26, 2021 at 21:47
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3 Answers
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This is a good question and it gets to the most basic foundations of immunology. Your immune system is made to be flexible - able to adapt to almost any challenge. However, with so much flexibility comes the potential to generate immune cells that react against the 'self'. So, at the other extreme, the immune system needs to be limited.
In order to meet these two (potentially conflicting) goals, immune (at least lymphocytes) cells have a two-step development pathway. In the first step, the body randomizes its immune receptor specificity. In the second step, it ensures that these receptors are not auto-reactive.
Doing so means that immune cells are aware of their environment at the time that they are 'born.' Take a look at this review from the Fuentes-Panana lab to read about how tumors actively cultivate the immune system of their host in order to maintain a more favorable environment.
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Great question and in part, you are correct. However, you must also remember that this greatly depends on what genes have undergone mutation.
In the case of cancer, it's usually either a gene that regulates cell proliferation rates, induces programmed cell death or helps to repair damaged DNA. When one (or all) of these genes is mutated, the cell constantly proliferates and/or does not die when it is "programmed" to do so or cannot repair mutations to it's DNA, thus creating a cancerous tumor.
Now, on to the immune system. The reason a persons immune system does not target and kill it's own cells is because of a certain set of genes that is specific to each and every person called Major Histocompatibility Complex (MHC). These genes encode specific cell surface molecules that the immune system cannot produce antibodies to bind to because they are "locked", if you will (see, the immune has a sort of built-in list of genes that code for antibodies that bind to different sequences of molecules (that's how you develop immunity and fight pathogens), the genes that code for the specific molecules that your cells have on their surface are just not on that list.) In order for a person's immune system to recognize cancerous cells as a pathogen and destroy them, the cancer cell's MHC genes would also need to be mutated drastically.
For instance, breast cancer is usually caused by a mutation in the BRCA1 or BRCA2 genes. These genes assist in DNA repair. Even if this mutation happens, these cells still have the same MHC as the rest of the cells in your body because BRCA1 and BRCA2 don't really have much to do with MHC. Because of this, the immune system does not recognize the cancerous cells as a threat and is unable to destroy or even detect them.
I hope this answers your question.
CDB
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1$\begingroup$ This is very wrong. T-cells recognize MHC + peptide combinations. Immunogenic mutations in non-MHC genes can drive an anti-tumor response. $\endgroup$ Commented Aug 15, 2015 at 19:25
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$\begingroup$ Did I fail to convey this? Perhaps my wording was confusing. I meant that most main CANCER causing genes do not cause a major change in the surface molecules of the cell. However you are correct, some genes that are not considered MHC linked genes can affect this, but most are not cancer causing. $\endgroup$– CDBCommented Aug 15, 2015 at 19:45
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1$\begingroup$ It reads as if you completely misunderstand how the MHC-T-cell interaction works. MHC class I molecules on the cell-surface are loaded with the peptide fragments from intracellular proteins degraded by the proteasome. In infection, this can be proteins from viruses or microbes that are recognized as foreign. In cancer, this can be mutations that generate a peptide with novel structure. Many mutations, especially deletions, but also many oncogenic point mutations do not necessarily generate novel immunogenic peptides. $\endgroup$ Commented Aug 15, 2015 at 20:17
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$\begingroup$ I apologize for not explaining this concept very well. It would seem, if you were that confused, I have failed completely at explaining it. I have done my best to explain and it is understandable to me, so I do not know how to clarify. Please, if you can explain more efficiently, feel free to edit my answer. $\endgroup$– CDBCommented Aug 15, 2015 at 20:35
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$\begingroup$ If a cell's apoptosis mechanism is not functioning would this disrupt or cause to malfunction the MHC in the cell? $\endgroup$– 201044Commented Aug 16, 2015 at 0:10
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Answering your two questions together, all cells enjoy many mechanisms that try to prevent the mutated ones from surviving. During the cell cycle of somatic and germinative cells, for example, there are three moments of verification in which the cell will undergo a kind of internal "check up". During the interphase, this process takes place between phases G1 and S and also at the end of phase G2. In the division, as soon as the interphase ends, there is also one more verification. If during one of these three steps any mutation is recognized, the cell will undergo apoptosis (regardless of whether the identified mutation(s) were in fact to induce a neoplasm in the tissue or not.
Now, if even with these three checks any or some mutations go unnoticed, the cell in question will go through cell division and the mutation(s) will be inherited by the new lineage that will follow; but this does not indicate that the cell will be cancerous, because for a cancer to develop it is necessary for specific mutations to occur in specific genes.
This was just some information I wanted to give you, now answering your question more directly: cancers as a whole enjoy very cunning mechanisms that aim both to make tumor cells indistinguishable from normal cells for the immune system as well as they try to make it very difficult for the many proteins of the Complementary System, which is a vital part of the recognition of abnormalities of the Immune System, to get closer. There are many mechanisms that tumor cells enjoy, but one that stands out is what is called the Malburg Effect. This effect, described by the German physician Otto Walburg, in the 20th century, in a simplified way, consists in the fact that cancer cells consume a much higher amount of glucose than healthy cells and still convert a good portion of this glucose into lactose. This considerable production of lactose makes the environment around the tumor or neoplastic tissue more acidic than usual, acidic enough to compromise the activity of the many proteins that play a role in recognizing abnormalities in the immune system. This is one of the many mechanisms that many cancers use, which, directly or indirectly, makes it difficult for the immune system to recognize it.
The Warburg Effect: How Does it Benefit Cancer Cells? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224
Another interesting point is that of the five existing therapies to treat cancers currently (chemotherapy, immunotherapy, target therapy, hormone therapy and surgery), immunotherapy consists precisely in "training" the immune system to know how to differentiate a cancer cell from a healthy cell . In a very simplified way, what they do is surgically remove a slide of your tumor or neoplastic tissue, identify the proteins present in the cell membranes of the cells that make up the collected material (among other molecules) and differentiate what is there only in the tumor. From the moment the tumor's own molecules are identified, a kind of vaccine is made, in order to introduce a cocktail with these tumor-specific molecules into the patient's body so that the immune system can then chase the tumor cells, knowing how to differentiate of healthy cells.
Cancer Treatment Vaccines - Immunotherapy - National Cancer Institute https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/cancer-treatment-vaccines
There is also an explanatory video, if I'm not mistaken from Nature, very good to introduce the idea in a very general way of how immunotherapy and cancer vaccines work: https://youtu.be/jDdL2bMQXfE
