Cytokines are small proteins that aid in intracellular signaling. They represent a group of immunotherapies that help stimulate the immune system in a broader sense.
Hematopoietic growth factors
To review from the “Basic Principles of Tumor Immunotherapy” module, cytokines are soluble proteins that facilitate signaling between cells and are largely produced by immune cells; cytokines may be involved in autocrine, paracrine and/or endocrine functions. These proteins play an important role in promoting immune cell growth and activity. Cytokines are classified into several functional groups, including interferons, interleukins, chemokines and hematopoietic growth factors. Cytokines have pleotropic effects which can facilitate both pro- and anti-tumor immune response. Functions of cytokines that aid in anti-tumor immunity are discussed below.
Robert L. Ferris, MD, discusses cytokines and their several functional groups.
Interferons are cytokines that are known for their antiviral activity as well as for their role in regulating immune activity. Interferons are divided into two groups: Type I (including interferon alpha and interferon beta) and Type II (interferon gamma). Currently, interferon alpha is the only interferon approved for the treatment of cancer; it can activate natural killer cells in addition to aiding in the proliferation of B cells, though its specific anti-tumor activity differs across cancer types. For example, B-cell regulation is thought to be an important anti-tumor mechanism of interferon alpha in non-Hodgkin lymphoma, but not in melanoma.
Interleukins are cytokines that function as intercellular signals between white blood cells (leukocytes), as their name suggests. Interleukin -2 was the first immunotherapeutic agent to effectively treat cancer in humans; it promotes rapid growth and proliferation of T cells, and is largely produced by CD4–positive T cells. In 1984, a woman with metastatic melanoma who had failed several lines of treatment received aggressive interleukin-2 infusion and had a complete response within months. To date, interleukin-2 remains the only approved interleukin therapy, though other interleukin family members are in clinical trials as single agents and as part of combination regimens for the treatment of various cancer types.
Chemokines are a group of cytokines that induce movement of surrounding cells through a process called chemotaxis. Using intracellular gradients and signaling , they can recruit and direct white blood cells for inflammatory and immune responses. The role of chemokines in tumor formation is twofold:
- Chemokines can limit tumor growth by recruiting white blood cells to the tumor site; or
- Chemokines can promote tumor growth by directing movement of cancer cells.
Hematopoietic growth factors
Hematopoietic growth factors are glycoproteins that induce differentiation and proliferation of progenitor cells. Granulocyte colony–stimulating factor, for example, is used to increase circulating neutrophils in patients whose white blood cell counts have been depleted by treatment with cytotoxic systemic chemotherapy.