Cancer immunology AMA

How important is the diet when dealing with cancer?

Hi Mr Jomo, thanks for your question. It is difficult to answer very specifically as we are just not smart enough in this area yet. Diet is clearly VERY important - our problem currently is that we just don’t know exactly what is the ‘right’ diet and it will very likely be individual to every person/every cancer.

Lots of work is going in to this area now - so we shall know more in the short term future, for sure.

What part of this job do you find the most "fun"? I ask because obviously your cause is super noble and important, but I know everyone always seeks enjoyment in their work.

Thanks for your question. Being a researcher is a hugely varied job - from being in the laboratory doing practical work to reading, analysing data and communicating your results.

Personally, I find the most fun is getting that hard-fought experiment to work in the lab and seeing the results for the first time. Exciting!

How universal are the restrictions on animal testing? Are some countries much better than others?

Restrictions and regulations on animal testing are universal. Having said that, specific rules are not universal and some countries have tighter control than others.

Using animals for research is strictly regulated in the UK and EU - here in the UK we have some of the most comprehensive restrictions in the world, which we in the research community really welcome as we want to work in an ethically correct way.

What are your thoughts on the recent reports in Israel showing progress on a cure for cancer within 1 year using a process called MuTaTo to target cancer and its mutations?

https://www.google.com/amp/s/nypost.com/2019/01/28/well-have-a-cure-for-cancer-within-a-year-scientists/amp/

https://www.dailywire.com/news/42759/still-want-boycott-israel-israeli-scientists-find-hank-berrien

https://www.google.com/amp/s/m.jpost.com/HEALTH-SCIENCE/A-cure-for-cancer-Israeli-scientists-say-they-think-they-found-one-578939/amp

I am not aware of any scientific publications about this as yet, which otherwise obviously sounds exciting. It will be a question of whether they can specifically target the cancer cells. We shall wait and see and cross our fingers.

Having had a littlebrother who died of braincancer, do you believe your research could be used to combat cancer types other than skincancers?

It is a devastating disease and I am really very sorry for your loss, Jacobstx! Our poor understanding of ways to treat brain cancers – relative to some other cancers – is definitely being recognised now. For instance, it is a priority area for Cancer Research UK. Hopefully this will encourage much more research and understanding of the disease and how to treat it!

Some of the pathways I am looking at in the skin may indeed also be relevant in the brain. I will investigate this with colleagues and neurologists that know more about our complex brain than I do. Collaboration is always key for research.

How come newer therapies like nivolumab can create other responses like inflammatory arthritis in a host? I'm baffled.

A drug like nivolumab is a new way to fight cancer - in that the drug does not target the cancer itself. Instead it targets an immune cell called a T cell and blocks a pathway that otherwise inhibits the T cells action. This will allow the T cell to attack the cancer cells.

However the T cells are now ‘free of inhibition’ and therefore may also induce exuberant responses against other targets - some of these being our own proteins, such as for example those in the joint as you mention.

Hello,

I'm not a scientist so these are going to be some very basic questions, sorry.

So you said you found IgE in mice protects them against the developpement of skin cancer and now you're going to investigate if the same is true in humans. How long does that process take? How long did you take to make this discovery in mice and how long do you think it will take you to verify that hypothesis in humans? And if it is true, what will be your next steps?

Also, you said that the protein IL-13 helps protect skin cancer initiation. Does that mean there is a way to get this protein naturally and thus to help protect ourselves against skin cancer? This remind me of when people say "X food is good at preventing Y cancer", how much of it is true? Is it scientifically proven that some food can reduce the risk of cancer? And how effective is it?

Thanks.

Every study builds on previous work, so it is often hard to say when one starts and the other ends. The IgE study you refer to builds on work we published in 2011 and then I worked on it for 6 years before I published on it again. It takes time…! However, we now know quite a lot so we know where to start looking in humans. I therefore believe we can make faster progress now.

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In regards to IL-13 - luckily we all have it in our skin all the time and my research shows that it can help protect us against development of cancer. Once a cancer has escaped this surveillance mechanism however - we do not know if it will be of help any longer. This is under further investigation.

Thanks for the reply!

Follow up question, how long would it take without animal research? Would it even be possible at all?

Of course very hard to say. Honestly, I think it may not have been picked up without being able to explore detailed mechanisms of immune cells within tissues, pre-cancer – something that is very difficult to do in humans unless you know what you are looking for beforehand.

Simple question from be. Do you believe cancer could totally be eradicated or immunised?

I do not think cancer can be totally eradicated unfortunately. Some cancers we will be able to immunise against or perhaps otherwise be able to enforce our resistance to - others we need to get better at treating.

It sort of sounds like you research tissue resident T cells. The papers you linked talk about gamma delta Tcells.

Why gamma delta over conventional T cells?

And how would a therapy using tissue resident T cells work? Do you inject them into the skin, into blood and they home to skin, how do you envision a therapy working?

Hi CytotoxicCD8 (interesting name btw!), I have indeed focussed quite a lot on gamma delta T cells in my work. That is because I am interested in epithelial cell (the cells that line our body surface tissues) - T cell interactions and how our body surfaces are protected.

Whilst gamma delta T cells are relatively rare in the blood (less numerous than conventional T cells) they are much more numerous in epithelial tissues, such as the gut or skin. Here they ‘live’ close to the barrier surface, in contact with the epithelial cells. We believe they form an important function in cancer immune surveillance by monitoring epithelial cell ‘health’.

What's your opinion on injecting polio and other diseases to cure cancer? Will this be a viable option in the future?

I do not think this is a viable option for the future. Incidentally this has been done in the past as far back as the late 1890s; a Dr William Coley discovered one of his patients with cancer was cured following a severe infection (first observation of the power of the immune system - before we even knew anything about it!). He then developed a ‘Coley’s toxin’ and was infecting his patients with certain bacteria.

This has been tried on and off over the decades and although it showed some success - it never proved consistently efficacious in clinical trials. I cannot see us going back to these kind of ‘unspecific’ immune stimulations now when we are much more knowledgeable about the immune system. We now want to get much better at targeting the cancer specifically.

What are your thoughts on:

1. intermittent fasting and the effects it may/may not have on eradicating cancer cells?
2. plant based whole food diets as it relates to helping minimize cancer risk?

There is really no consensus in the field as yet on either fasting or particular plant foods to prevent/eradicate cancer cells. There are lots of studies coming out and these studies get a lot of press attention as of course it is in everybody’s interest.

For now, we just know that eating a well balanced diet high in plant-based foods helps us stay healthy in general and therefore also may aid our continued cancer surveillance mechanisms.

Hi Dr Strid, in your paper you write:

How IgE inhibited tumor growth in our model remains to be determined; however, it required expression of FcεRI, and mast cells were not essential, which would suggest it might involve soluble factors and/or cytotoxicity mediated by basophils.

Can you suggest/guess a mechanism by which IgE assists in anti-tumor effects? My impression is that IgE is mostly an anti-parasitic antibody, and that cell-mediated immunity via Th1 CD4+ cells and natural killer cells were responsible for immune surveillance of cancer.

Thank you in advance for reading/answering my question.

Thank you for your question. You are right, Th1 immunity is the most studied and desired cell-mediated response against cancer cells. Studying IgE antibody responses in this context is a new approach. As you say, IgE is mainly thought to have evolved to protect us against parasitic infection such as worms and ticks. However, to be honest, we still know very little about the physiological role of IgE and it is curious if such and extremely fast and potent response really evolved to protect us only against these slowly replicating macroparasites.

Whatever the evolutionary reason for the persistence of this response, we now believe that it can also defend our bodies against the harmful effects of toxins and other cell damaging environmental xenobiotics (many of which can cause DNA-damage and possible cancer initiation). It may do this using similar mechanisms as during a tick bite - enhancing regeneration of the tissue and movement of affected cells up and out of the tissue.

In terms of cancer, this may mean that the DNA-damaged/mutated cells get ‘sloughed off’ before they are allowed to develop into a tumour. We are currently studying the mechanism of the anti-tumour effects in detail - so I can hopefully return with a qualified answer in the coming years!

What's going on with fasting and maybe keto diets for certain types of cancer? Have there been studies yet? I know many types of cancer feed on sugar so it seems this could be possibly be beneficial along with other treatment maybe

You are right sugar can be a good growth ‘medium’ for many cancers. However, this topic is extremely complex (please see my other answer to MrJomo) and much more research is required to understand the metabolism of both our health cells and cancer cells. This also ties in to all the new research on the microbiome… so a lot of complex work to understand!

What kind of animals do you use in testing?

Do you feel immune therapy is the future of cancer treatment rather than killing everything off with chemo?

Thanks for your question, Beachchair1. In my research group we only use mice if we need to do any animal testing. Mice are the experimental animal of choice as they have the lowest neurophysiological sensitivity while still having an immune system of comparable complexity to the human.

Are there other times when you want to experiment on another animal that is closer to a human, but can’t knowing the ethical implications? Are there talks to expand on animal medical testing for specific research?

For my kind of work, using mice as an experimental model will suffice and I do not want/need to use any ‘higher’ animal. A combination of this, information gained from using human tissue - and knowledge of the differences/similarities between human and mouse immunology gives me a good foundation to predict responses in human.

In general, talk in the scientific community is much more concerned on how we can reduce, refine and replace animal testing in our research - rather than expand. This is called the three R’s of ethical animal research and we all work with this in mind.

Your mention of IgE is interesting. Have you find the possible link of skin cancer and allergic reaction itself? Do people who have allergy more susceptible to skin cancer or the other way around

Thank you for your question. A possible link between allergic disease and cancer is something that has intrigued researchers for decades. Many epidemiological studies have attempted to look at this - and many different ‘answers’ have been found.

Most of these studies are retrospective studies, for example asking cancer patients whether they have suffered from an allergy - this kind of data can be very difficult to interpret. Both allergic diseases and cancer are complex multifactorial diseases (and not just one disease) so one needs to be careful with these studies.

Nevertheless, the epidemiological data does point towards links between allergic disease and cancer - particularly there seems to be an inverse association between allergies and cancer of body surface organs (i.e. skin, gut, cervics etc), suggesting having an allergic type response may be protective against cancer in these organs.

Our own studies on IgE and skin cancer are among the few, for now, that show a causal link between a molecule normally associated with allergy - and cancer protection.

So is your research leaning more towards the prevention aspect of skin cancer or the treatment of cancer that has already been detected? In your opinion, which of these do you believe to be the most important in terms of where cancer research is at right now?

I came to cancer research from being interested in how the immune system detects tissue damage - so I have so far been mainly focussed on understanding immune responses to very early signs of cellular dysregulation.

This kind of interaction is often long before a tumour develops, so you can say I have been focussed on prevention. However, we are of course also interested in whether some of the same pathways can be used for treatment.

Do you think there is anything that humans have incorporated into daily life that could be increasing the risk of cancer? Eg technology, food. Etc

The highest risk factor for developing cancer is age - and we do not want to get rid of that! Having said that, I think there are many things in our daily life that could increase the risk of cancer - like air pollutants being inhaled and sticking on our skin, chemicals in our cosmetics and food, our obsession with cleaning and scrubbing ourselves thus lowering our body surface defences etc etc.

It’s a minefield - but luckily our bodies have many coping mechanisms and most pre-cancer lesions will be dealt with before they are allowed to develop into any clinically apparent disease.

Do people with darker skin get more often skin cancer?

No they do not. People with darker-coloured skin do get skin cancer but at a reduced frequency. UV-irradiation from the sun is a major cause of DNA-damage and mutation in the skin - some of which can lead to skin cancer. Darker-coloured skin is less sensitive to UV-irradiation.

Having said that, people with darker-coloured skin still do need to protect themselves as they can clearly still develop all forms of skin cancer. In addition, a recent study showed that people of dark skin colour were more likely to be diagnosed with melanoma in its later stages and (probably therefore) had the worst prognosis with this disease.

Do you see a future where animal testing would be totally eradicated from research? What kind of models are promissing?

Thanks for this important question, Nyrthak. Techniques to study human cells are becoming much more sophisticated, so we can get a lot more in depth knowledge from that approach. Similarly, machine learning, mathematical modelling and in silico techniques are also offering us ways of cutting down the number of animal testing needed.

The research community is making concerted efforts to reduce the use of animals as much as possible. But for now the complexity of the interactions that goes on in a live organism is still needed to fully understand what happens when we develop treatments for a disease like cancer.

Hello,

Can you please explain what exactly γδ T cells are?

Thanks!

Hi, yes sorry sounds more technical than it is: There are two kind of T cell receptors, which define a T cell - one made up of an alpha and beta chain (ab T cells) and one made up of a gamma and delta chain (gd T cells).

In human (and mice) ab T cells are the main T cells in the blood whereas gd T cells are the main T cell in some body surface organs (e.g. skin and gut). Interestingly the ratio of ab T / gd T cells varies a lot across different species - chickens and pigs for example are full of gd T cells!

Does never wearing sunscreen means you will get skin cancer for sure?

Thanks for your question. To answer: no it doesn’t. Although blocking irradiation clearly does reduce the potential of picking up mutations in your skin. Actually we all harbour a lot of ‘cancer’ mutations even in healthy skin but these are kept in check and most likely never develop into a cancer.

We know the immune system is very important in this surveillance checkpoint - patients on systemic immune suppression are 100-150% more likely to develop skin cancer.