Does the immune system go inside of tumors?

[Steven Ellet]

Does the immune system attack diseases inside a tumor (cancerous or otherwise)?

 

[Astronuc]

Does the immune system attack diseases inside a tumor (cancerous or otherwise)?

Not necessarily, and probably more often not. This is the reason for the development of immunotherapy.

As explained at cancer.org

Clearly there are limits on the immune system’s ability to fight cancer on its own, because many people with healthy immune systems still develop cancer:

• Sometimes the immune system doesn’t see the cancer cells as foreign because the cells aren’t different enough from normal cells.
• Sometimes the immune system recognizes the cancer cells, but the response might not be strong enough to destroy the cancer.
• Cancer cells themselves can also give off substances that keep the immune system from finding and attacking them.

To overcome this, researchers have found ways to help the immune system recognize cancer cells and strengthen its response so that it will destroy them. In this way, your own body is actually getting rid of the cancer, with some help from science.

https://www.cancer.org/treatment/tr...ypes/immunotherapy/what-is-immunotherapy.html

 

[immunology guy]

Does the immune system attack diseases inside a tumor (cancerous or otherwise)?

It depends. It's thought that tumors develop all the time but the immune system monitors for them and kills them ("immune surveillance"). For a tumor to develop it has to learn to escape this immune response ("immunoediting"). It does this in a number of ways - modulating cell surface antigens, secreting immunosuppressive cytokines and other factors, recruiting immune-suppressive cells, etc., etc. The number of ways tumors use is extensive. Some tumors are less successful and are called "hot tumors" because they are filled with immune cells. These tumors are the ones that are successfully treated with checkpoint inhibitors that can reactivate those immune cells. Others are pretty much devoid of immune cells and are called "cold tumors". The current challenge is turning cold tumors hot so the immune system can eradicate them.

 

[berkeman]

@Ygggdrasil

 

[Steven Ellet]

To clarify, I’m not asking if the immune system attacks tumors. I’m asking if a disease (such as the common cold) will go unchecked in a tumor.

 

[Ygggdrasil]

To clarify, I’m not asking if the immune system attacks tumors. I’m asking if a disease (such as the common cold) will go unchecked in a tumor.

There are a few issues to consider here:

1) Most viruses infect only a specific subset of cells in the body (e.g. SARS-CoV-2 can infect only cells expressing the ACE2 receptor and, because of how it is transmitted, tends to only infect cells in the respiratory system [if the immune system fails to stop the infection from spreading beyond there, this is when you start getting severe problems]), so viruses would be limited to only infection certain types of cancer cells.

2) In general, viruses can infect cancer cells, and some are exploring this as a means to develop oncolytic viruses (viruses that selectively infect cancer cells but not non-cancerous cells).

3) While tumors do evolve means to evade the immune system (the post from @Astronuc has a nice link discussing this phenomenon), I think most of these mechanisms are specifically to stop the immune cells from attacking the tumor cells and not generally to turn off the immune system in general (though I am not as expert in this area, so please correct me if I am wrong).

4) People being treated for cancer are often a greater risk of infectious diseases not because viruses can spread rapidly in tumors, but because chemotherapy often suppresses the immune system (many drugs that target the rapidly dividing cells inside of a tumor also target the rapidly dividing cells in the immune system), so this is a larger concern for infectious disease in individuals with cancer.

In general, the interplay between tumors and the immune system is a very active area of research in cancer biology and immunology. If you are interested in the topic, you could look up papers on the "tumor microenvironment" or "tumor immune microenvironment." Cancer is not a single disease (and even different tumor of the same type or different tumors within the same individual can be very different), so exactly how a tumor influences the immune cells in its vicinity can differ widely between different types of tumors (as @immunology guy mentioned with his example of "hot" vs "cold" tumors).

 

[Astronuc]

2) In general, viruses can infect cancer cells, and some are exploring this as a means to develop oncolytic viruses (viruses that selectively infect cancer cells but not non-cancerous cells).

I have heard about this research. For example - https://www.usnews.com/news/health-news/articles/2019-07-05/study-strain-of-common-cold-virus-could-cure-bladder-cancer

https://pubmed.ncbi.nlm.nih.gov/16555996/

https://www.jstor.org/stable/4450511 (the idea has been around for several decades)

More recently - https://www.salk.edu/news-release/use-the-common-cold-virus-to-target-and-disrupt-cancer-cells/

I’m asking if a disease (such as the common cold) will go unchecked in a tumor.

So, one is asking if a virus could enter tumor cells, replicate and spread?

I would image if a virus could enter a cancer cell without significantly modifying the surface, it could possible escape the immune system. But I believe viruses to modify the outer surface of cells, including tumor cells, so in theory, they could be attacked by the immune system.

There are studies on retroviruses being responsible for causing cancers.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925786/

With regard to SARS-Cov-2, there are studies looking at the virus and its effects on cancers, for example: COVID-19–Induced Modifications in the Tumor Microenvironment: Do They Affect Cancer Reawakening and Metastatic Relapse?
https://www.frontiersin.org/articles/10.3389/fonc.2020.592891/full

Immune mechanisms in cancer patients that lead to poor outcomes of SARS-CoV-2 infection
https://pubmed.ncbi.nlm.nih.gov/34871809/

Respiratory viruses are a complication for cancer patients.

Infections are a major complication of cancer and its treatment. Community acquired respiratory viral infections (CRV) in these patients increase morbidity, mortality and can lead to delay in chemotherapy. These are the result of infections with a heterogeneous group of viruses including RNA viruses, such as respiratory syncytial virus (RSV), influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (HMPV), rhinovirus (RhV), and Coronavirus (CoV). These infections maintain a similar seasonal pattern to those of immunocompetent patients. Clinical manifestations vary significantly depending on the type of virus and the type and degree of immunosuppression, ranging from asymptomatic or mild disease to rapidly progressive fatal pneumonia Infections in this population are characterized by a high rate of progression from upper to lower respiratory tract infection and prolonged viral shedding.

The main concern seems to be that a severe infection may lead to a fatal pneumonia in someone whose system is already compromised.

 

[Steven Ellet]

So, one is asking if a virus could enter tumor cells, replicate and spread?

Exactly, my idea was to first give the patient a virus/bacteria to get the system to recognize the pathogen, then when they are cured of it, inject it into the tumor and let it run wild.

 

[Laroxe]

Apparently viruses don't actually cause cancer though they set cells on the path, its suggested that around 20% of cancers can be associated with viral infections. This is Prof. Vincent Racaniello talking about it.

The fact that a virus enters a cell doesn't actually mean it can evade our immune system, individual cells have their own defences against infection. While cancer cells can appear to develop new abilities this often comes at a cost, cancer cells can lose the many of the abilities of functional cells. It's important to consider that cancer cells in a tumour become increasingly varied, they are not of a single type. Some of these cells may lose the normal defences against infection, therefore becoming more susceptible to infection, this seems to be the case with the measles virus.

One of the problems is in identifying which tumours have a sufficiently large population of cells with impaired defences and to which viruses.

The variability in the cancer cells may also affect the way in which they signal their abnormality to the immune system, generally cancers have already developed ways of evading immune surveillance, some cells may also over express signalling chemicals which suppress immune cells or which reduce the effectiveness of chemicals which induce apoptosis.

A response to any viral infection may reduce the level of immune tolerance, this can have an impact, even on distant tumours, but viral infections in an immune competent person are often cleared before the virus has done its job. There may be advantages in using oncolytic viruses at the same time as chemotherapy, which suppresses parts of the immune system or in combination with one of the new biologic drugs which can reduce the tumours' ability to evade immune surveillance. As the immune system is responsible for removing dead cells, if there are a large number it does learn to selectively target the cell types. Again, using combinations of treatments like radiotherapy can sensitize the immune system to the cancer cell types and increase the effectiveness of other interventions. Even damaging the cells might reinforce the effects of apoptosis.

While the effects of viral infections has been known for many years it seems that we will need to wait on engineered viruses that are more specific, predictable and less likely to induce systematic adverse effects, these are just starting to become available and are often best used with other approaches. While virus infections have been associated with "miracle cures", because of the huge variability in tumour cells and types it's likely that in most cases they will represent an adjuvant therapy. However, as cancer management is increasingly seen as representing long term control, it still represents a treatment with massive potential.