How our genes, microbiome and environment can influence the cancer-immune setpoint

In our second post exploring the different types of factors that can influence a person’s cancer-immune profile, we look more closely at the host genetics, microbiome and environmental factors.
How our genes, microbiome and environment can influence the cancer-immune setpoint

As part of their seminal paper proposing the cancer-immune setpoint, Chen & Mellman set out all of the factors identified so far that can influence an individual’s cancer-immune setpoint. They grouped these according to their type – tumour genetics, host genetics, the microbiome, the environment and therapeutic agents.

My previous post looked more closely at a tumour’s genetics and epigenetics. In part two, we explore the other factor types in more detail and find out how they can influence an individual’s cancer-immune setpoint.

Host genetics

  • Variations in genes involved in the immune response are likely to contribute to the tumour immune profile, and to an individual’s cancer-immune setpoint.
  • The list is likely to include genes encoding TLR4, TNF-α, NF-κβ, FcγRIII, NOD2, ATG16, JAK/STAT or inflammasome pathway proteins, which are involved in controlling different aspects of the immune response and inflammation.


  • The gut microbiome is likely to play an important role in the response to immunotherapy treatment, which is supported by evidence from mice experiments demonstrating that defined species of gut bacteria help enable anti-tumour responses after treatment with anti-PD-L1/PD-1 or anti-CTLA4 therapies.
  • Assuming this is also applicable in humans, a person’s gut microbiome may be important in determining both the baseline immune profile of a tumour – as well as an individual’s cancer-immune setpoint.

Environmental factors

  • Our immunity can be affected by several environmental factors, including infectious agents, diet and pharmaceuticals.
  • An example of a pharmaceutical that could potentially have an impact are the cholesterol-lowering statins, as there is some evidence suggesting that taking these drugs is associated with a lowered immune response.
  • Intriguingly, exposure to sunlight may influence immunity (known as photoimmunity) – and conceivably, low sunlight conditions may correlate with a more inflammatory environment, and in turn, a better response to immunotherapy.
  • Although not strictly an environmental factor, alterations in immune function due to age may also be an important variable in determining an individual’s cancer-immune setpoint.

You can explore all of the factors that have been proposed so far on our interactive framework. But it needs to continually evolve as new data are published.

Chen & Mellman state in their review, “It should be noted that this representation is only a partial list and that factors will be added, removed or modified in the future.”

We want to accelerate its evolution through a crowdsourcing of ideas from the community. But this requires your help. Please go to the framework to add or comment on existing factors – or suggest new ones.

To help get you started, please follow our a simple step-by-step guide in our ‘how to’ post.