A landmark study (Anke Sparmann & Dafna Bar-Sagi, 2004) established the link between oncogenes and cytokines. Using a xenograft mouse model, the authors demonstrated that interleukin-8 (IL-8, also called CXCL-8), a pro-inflammatory cytokine molecule, was the transcriptional target of oncogene Ras. The authors also provided cogent evidence that Ras-dependent IL-8 activity was required for tumor-associated inflammation and new blood vessel formation.
This is in line with observations that chronic inflammation can lead to carcinogenesis over time. Examples include hepatitis B and hepatitis C leading to hepatic cancer, chronic H. pylori infection leading to gastric cancer, and chronic HPV infection leading to cervical cancer.
How do cancer cells use inflammation for growth and survival advantage? During the normal inflammatory response by the innate immune system, phagocytes such as macrophages carry out their designated task of engulfing and destroying infected cells. These same macrophages, under cancerous conditions, become "corrupted" by cancer cells. As a result, instead of phagocytosing cancer cells, the macrophages differentiate into "tumor-associated macrophages" (TAMs). These TAMs promote immune suppression by secreting PD-L1 to interact with PD-1 on CTL, leading to CTL inactivation and providing a comparative survival advantage for cancer cells.
Macrophages that reside in the brain and spinal cord (which together constitute the central nervous system, CNS) are called microglial cells. Similar to macrophages residing in other tissues and organs in other cancers, microglial cells are also "corrupted" by brain cancer cells such as glioblastoma (more will be discussed later).
The oncological consequences of TAMs and other cancer-associated immune cells are dire; they serve as "added fuel" in promoting tumor cell proliferation, angiogenesis, and migration.