Anatomy, illustrating chronic inflammation (Wellcome Images)
Chronic inflammation

It’s pretty well-established now that the immune system can, and normally does, protect us against cancer. In particular, the adaptive immune response (especially T cells) clearly limits cancer growth, so that the only cancers we can detect clinically are those that have developed defenses against the adaptive immune response (see here for more).It seems paradoxical, then, that the immune response may also help cancers develop. However, there is a fair bit of evidence that a chronic immune response can actually help drive cancer development. This is especially true for the innate immune system, but long-term stimulation of the adaptive immune system may also be carcinogenic.

The role of the innate system is relatively easy to understand (at least, it made sense to me, which is no guarantee that it makes sense). Chronic inflammation is a bad thing — there are lots of checks built in to the immune response to try to prevent that — and conditions where there’s chronic inflammation are often clearly associated with cancer. The example that jumps to my mind is hepatitis B infection. As far as I know, it’s not generally believed that the virus itself is carcinogenic per se (that is, in contrast to things like Kaposi’s Sarcoma herpesvirus, or some human papillomaviruses, which seem to have the ability to drive infected cells into a de-regulated state). Rather, the increased risk of cancer associated with HBV infection (about five to fifteen times higher than the general population) is probably because of the chronic inflammation that the virus infection causes. 1

There are a number of ways the chronic inflammation can lead to cancer. Simply increasing cell turnover (as cells are killed by the inflammation and have to be replaced) increases the chance of a dangerous mutation arising. Inflammatory factors can act as growth factors for tumor cells. Reactive oxygen species produced as part of the inflammation may increase mutation frequency. And so on. 2

Inflammation and angiogenesis are hallmarks of squamous carcinogenesis in HPV16 transgenic mice.
Inflammation in carcinogenesis

It’s a little more surprising to contend that the adaptive immune system may also help drive cancers. My first response to the concept was to dismiss it, because immune-deficient mice actually have more tumors than wild-type mice, not fewer. However, as I realized within ten seconds of my dismissal, that’s not counterevidence; adaptive immunity could drive cancer at one stage and protect against it at another stage, and the experiments in question would only reveal which of the processes had the larger effect. And in fact, it turns out that although immune-suppressed people (AIDS patients, or transplant recipients) have increased risk of many tumors, they are at reduced risk of other kinds. For example, prostate tumors are less frequent in AIDS patients than in matched controls,3 and breast cancers are less common in transplants recipients4

I don’t think the mechanism(s) underlying this are as well understood as for innate immunity (and that itself is still not well understood). It’s likely that adaptive immunity plays a part in establishing some forms of chronic inflammation. In any case, there’s a fair bit of interest in blocking inflammation during cancer as a component of treatment.

It’s worth emphasizing that the great majority of tumors — if they show any change in incidence in immune-suppressed people — are more frequent; it’s just a few types of tumors that are less frequent. Don’t go immune-suppressing yourself in an attempt to avoid cancer.

  1. There are some virus factors that might be more directly correlated with cancer, but the link is rather indirect.[↩]
  2. Here’s a nice review:de Visser, K.E., Eichten, A., Coussens, L.M. (2006). Paradoxical roles of the immune system during cancer development. Nature Reviews Cancer, 6(1), 24-37. DOI: 10.1038/nrc1782[↩]
  3. Frisch, M., R. J. Biggar, E. A. Engels, and J. J. Goedert. 2001. Association of cancer with AIDS-related immunosuppression in adults. JAMA 285: 1736-1745.[↩]
  4. Stewart, T., S. C. Tsai, H. Grayson, R. Henderson, and G. Opelz. 1995. Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation. Lancet 346: 796-798.[↩]