What are cytokines, and how are they used in cancer treatment?

Cytokines are signaling proteins that are produced by white blood cells. They help mediate and regulate immune responses, inflammation, and hematopoiesis (new blood cell formation). Two types of cytokines are used to treat patients with cancer: interferons (INFs) and interleukins (ILs). A third type, called hematopoietic growth factors, is used to counteract some of the side effects of certain chemotherapy regimens.

Researchers have found that one type of INF, INF-alfa, can enhance a patient’s immune response to cancer cells by activating certain white blood cells, such as natural killer cells and dendritic cells (3). INF-alfa may also inhibit the growth of cancer cells or promote their death (4,5). INF-alfa has been approved for the treatment of melanoma, Kaposi sarcoma, and several hematologic cancers.

Like INFs, ILs play important roles in the body’s normal immune response and in the immune system’s ability to respond to cancer. Researchers have identified more than a dozen distinct ILs, including IL-2, which is also called T-cell growth factor. IL-2 is naturally produced by activated T cells. It increases the proliferation of white blood cells, including cytotoxic T cells and natural killer cells, leading to an enhanced anticancer immune response (6). IL-2 also facilitates the production of antibodies by B cells to further target cancer cells. Aldesleukin, IL-2 that is made in a laboratory, has been approved for the treatment of metastatic kidney cancer and metastatic melanoma. Researchers are currently investigating whether combining aldesleukin treatment with other types of biological therapies may enhance its anticancer effects.

Hematopoietic growth factors are a special class of naturally occurring cytokines. All blood cells arise from hematopoietic stem cells in the bone marrow. Because chemotherapy drugs target proliferating cells, including normal blood stem cells, chemotherapy depletes these stem cells and the blood cells that they produce. Loss of red blood cells, which transport oxygen and nutrients throughout the body, can cause anemia. A decrease in platelets, which are responsible for blood clotting, often leads to abnormal bleeding. Finally, lower white blood cell counts leave chemotherapy patients vulnerable to infections.

Several growth factors that promote the growth of these various blood cell populations have been approved for clinical use. Erythropoietin stimulates red blood cell formation, and IL-11 increases platelet production. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) both increase the number of white blood cells, reducing the risk of infections. Treatment with these factors allows patients to continue chemotherapy regimens that might otherwise be stopped temporarily or modified to reduce the drug doses because of low blood cell numbers.

G-CSF and GM-CSF can also enhance the immune system’s specific anticancer responses by increasing the number of cancer-fighting T cells. Thus, GM-CSF and G-CSF are used in combination with other biological therapies to strengthen anticancer immune responses.