From our lecture on tumor immunology we focused on how components of the immune system fight tumor progression. Clearly the immune system is very important in this regard, and people with compromised immune systems have higher incidence of cancer. The immune system is not always beneficial though. There is a body of work that suggests a pro-tumorgenic role for macrophages in cancer progression.
The theory is that macrophages initially fight cancer cells but then can become subverted by the tumor to actually become tumor promoting. In many human tumors, a high number of infiltrating macrophages correlates with a poor prognosis. Tumors are actually able to attract macrophages through the release of various chemotactic agents. Molecular studies have elucidated many protumoral functions macrophages carry out once at the tumor. These are mediated through the improper release of various cytokines. One protumoral function is the expression of growth factors which increase the growth rate of cancer cells. Macrophages have also been show to release signals that promote the formation of blood vessels in the tumor which is a necessary step for tumor progression. Macrophages are also capable of suppressing adaptive immunity.
This theory initially seemed very unlikely to me since we usually associate the immune system with fighting disease but taken together with what we have learned about how macrophages work, it makes more sense. There is normally a division of labor with T cells recognizing a danger and then instructing macrophages to remove it. With this is mind, it is less of a stretch to see how a different cells type (ie. a tumor cell) could step in and instruct a macrophage to act much differently. In fact, one of the phenotypes of the macrophage protumorgenic switch is a reduction in IL-12. We have learned that this cytokine favors a Th1 T cell which in turn makes macrophages ‘angry’.
If you would like to learn more about this research, there are many reviews available. A few are listed below:
1. Ostrand Rosenberg. Immune surveillance: a balance between protumor and antitumor immunity. Current Opinions in Genetics and Development. 2008. 18:11-18.
2. Mantovani, Alberto et al. The inflammatory micro-environment in tumor progression: The role of tumor associated macrophages. Crit. Rev. Oncol./Hematol. 2007. 10:1016.
3. Eremin, O et al. Tumor-associated macrophages (TAMS):disordered function, immune suppression and progressive tumour growth. J.R Coll. Surg Edinb. 2000 Feb;45(1):1-16
09 December 2008
The Tumor Promoting Role of the Immune System?
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2 comments:
It was counter intuitive to myself as well that the more macrophages there are, the more effective the tumor is at surviving. It is interesting that one mechanism the tumor uses to survive is to reduce the levels of IL-12. I wonder if this has been tested as a therapy to allow the macropahges' natural defenses to kick in by providing IL-12 to the tumor.
I just did a quick google search on whether IL-12 has been used for therapy and it appears it has: http://www.mpip.org/articles/Lotze.html
They used gene therapy of IL-12 to try to treat cancer and found a reduction in tumors in 28% of patients.
The study is from quite some time ago so I'm curious what has been done since then or what became of the study.
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