Chilly temperatures help cancers grow

19 November 2013 by Stephanie Swift, posted in Disease, Immunology, Medicine, Science

At low temperatures, the human body has a hard time. As the cold sets in, blood vessels constrict to maintain heat and some body parts – like fingers and toes – begin to suffer. Metabolism ramps up to fight the cold and shivering sets in. As these conditions continue, everything becomes sluggish as the cells of your body do not work as well. The body enters a state of thermal stress and only the most vital systems, like the brain, are left switched on.

Now, in a paper just published in the Proceedings of the National Academy of Sciences, Elizabeth Repasky at Roswell Park Cancer Institute in the US and colleagues suggest that cold has yet another disadvantage – it changes the way cancer cells grow and spread, at least in mice. This raises interesting questions about cancer therapies and many cancer studies, which tend to use mice as animal models.

Repasky found that mice living in a relatively cold environment (around 22°C) had cancers that grew more quickly and aggressively than mice living at a nice thermally comfortable temperature (around 30°C). A cold environment boosted the growth of several different types of cancer, including breast, skin, colon, and pancreas.

It did not matter if mice had lived in the cold for a lifetime before they got cancer—a chilly exposure even after their cancer had become established still made their tumours grow more quickly.

The body’s anti-cancer responses are mostly driven by the immune system’s T cells, which recognise and destroy tumor cells based on the altered proteins they produce. Tumours often react to a T-cell attack by producing signals that trick the body into suppressing these immune cells. This battle continues until one side outpaces the other – a lot of anti-cancer treatments given in the clinic help to swing the balance in favour of the immune system.

Both the cold and the comfortable mice had the same numbers of potential cancer-fighting T cells when they were healthy. But the tumour-seeking T cells in the comfortable mice were quicker and better at burrowing into the tumour to attack it. They also secreted more cancer-fighting substances than the cells from cold mice.

In the tumours of cold mice, there were greater numbers of suppressive cells capable of shutting down normal immune responses. Cold temperatures, then, shifted the body’s response from fighting the tumour to accepting it.

Most animal research facilities follow the same housing guidelines, and thus keep mice at colder-than-comfortable temperatures. This could introduce a systemic bias to animal testing where studies are done in conditions that aren’t entirely relevant. For example, what if you were trying a therapy that boosted immune function but did it in mice whose immune function was naturally tamped down? You might see no effect, when it could still be a useful drug. In contrast, something that causes tumour DNA damage might not have the same problem.

Cancers are cold

When we feel cold, we engage in warming behaviours – turning the thermostat up a notch, or thriftily putting on an extra layer of clothes. Mice are exactly the same – if they feel cold, they move to a warmer spot. When healthy mice get to choose what temperature they want to hang out at, with options at 22, 28, 30, 34 or 38°C, they typically migrate into the comfortable 30°C room. Mice with tumours tend to choose the hottest 38°C room. Cancer patients also commonly report suffering deep chills, especially following treatment.

It’s possible that growing tumours may induce a cold stress that probably promotes their own survival. We do not know exactly how this works yet, but this research still has important implications for cancer patients and their treatments. Could administering cancer therapies in a sauna – like setting improve their tumour – fighting potential and slow cancer growth?

Such approaches have been tried in small trials for breast cancer, angiosarcoma and sarcoma. They show that increasing body temperature to a mild fever over the course of a few hours improves response rates to radiation therapy.

Without large-scale studies no firm conclusions can be drawn, but this evidence suggests that the benefits of heat therapy for cancer may have been overlooked. Perhaps it is time we paid heed to the words of the ancient Greek physician Hippocrates:

Those who cannot be cured by medicine can be cured by surgery. Those who cannot be cured by surgery can be cured by heat. Those who cannot be cured by heat are to be considered incurable.

Originally published on The Conversation UK.

5 Responses to “Chilly temperatures help cancers grow”

  1. scilogs_paige Reply | Permalink

    Wow, is this something that has been suspected in previous research findings, or a brand new finding? Would like to know the methods / limitations of that paper, as well as the robustness of these findings - would seem that they have strong implications!

  2. Kevin Reply | Permalink

    The fact that some chemotherapy drugs induce chills or feelings of deep cold has nothing to do with this fact of tumours growing better in the cold and everything to do with the direct side effects of chemotherapy agents, and even more to do with the bodies reaction to large numbers of cells, tumour cells and many other types of fast multiply cells, dying and spilling their contents into the intercellular space. This stuff (that spills out of cells when they are killed) has all sorts of effects on the body. The stuff that comes out of white bloods cells in particular can have all sorts of effects on the physiological function of the body, and as they are swimming in the blood stream the spread these chemicals, many of which are immunomodulatory and are normally only released to have effects at specific sites of infection or inflammation, throughout the body. There is also the fact that chemotherapy drugs are commonly administered in 500 to 2000 mL of saline or 5% dextrose IV solutions, as well as given additional IV fluids for hydration during chemo administration. These fluids are generally at room temperature, which is 12 to 15 degrees C below body temperature. This alone can make one feel cold.

    I am not saying anything about whether cold has anything to do with the spread of tumour burden, but the fact that receiving chemotherapy leaves many patients feeling cold is an unrelated fact. It is not like the tumours, upon learning that they are about to suffer an onslaught of toxic medication, suddenly decides to cool the body to save itself.

  3. Stephanie Swift Reply | Permalink

    Hi Kevin,

    Thanks for your comment. You're absolutely right in saying that one of the side effects of chemotherapy is a huge amount of immune cell death and a subsequent release of nasty cell contents that can cause bodywide reactions, including the initiation of an immunosuppressive state.

    Yet the tumour itself, even without treatment, secretes cytokines that can not only induce immunosuppression, but can also act on thermoregulatory pathways. It is conceiveable, then, that tumours drive changes in the body's internal thermostat to further suppress immune cell function and promote their own survival. Hope this helps!

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