From TGF-beta to cancer therapy.
This article will introduce a novel concept in the use of TGF-beta insensitive host immune cells in cancer therapy. TGF-beta is a multi-functional cytokine. At a cellular level, it mediates cellular proliferation, growth arrest, differentiation and apoptosis. Because of the above cellular effects, TGF-beta is able to regulate a host of patho-physiological events in vivo, such as normal embryonic development, angiogenesis in tumor tissues, malignant transformation and immune surveillance. As a general rule, its direct effect on cancer cells is inhibition to cancer growth. However cancer cells are able to acquire the ability to evade this inhibitory effect of TGF-beta by becoming insensitive to TGF-beta. Furthermore, these malignant cells are able to produce large quantities of TGF-beta. The consequence of over expression of TGF-beta by cancer cells is an important factor for subsequent tumor progression. The excess amount of TGF-beta promotes tumor angiogenesis and immune suppression. The latter effect of TGF-beta is the most devastating to the host. The present discussion is focused on the role of TGF-beta insensitive immune cells in cancer growth. The host immune system offers a natural defense program against cancer. But, this natural immune surveillance is rendered ineffective by an overproduction of TGF-beta derived from the tumor cells. Rendering the host immune cells insensitive to TGF-beta in a gene therapy program offers a hope for us to successfully combat against cancer. Based on the above discussion, it is encouraging that there is a possibility for us to achieve a cure in cancer using TGF-beta insensitive immune cells in gene therapy.
Huang
Xuemei
X
Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Lee
Chung
C
D000818:Animals; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta