An overview of IL-7 biology and its use in immunotherapy.
Interleukin (IL)-7 is required for T-cell development as well as for the survival and homeostasis of mature T-cells. In the thymus, the double negative (DN) CD4(-) CD8(-) thymocyte progenitor transition into double positive CD4+ CD8+ cells requires Notch and IL-7 signaling. Importantly, IL-7 seems to have a dose effect on T-cell development and, at high doses, DN progression is blocked. Naïve T-cells in the thymus, and after their exit to the periphery, are dependent on IL-7 and TCR signaling for survival. Upon antigen exposure, they proliferate and differentiate into memory T-cells. Because IL-7 intervenes at all stages of T-cell development and maintenance, it has been introduced recently into clinical trials as an immunotherapeutic agent for cancer patients (of particular note, those who had undergone T-cell depleting therapy) in an attempt to increase their population sizes of CD4+ and CD8+ cells overall, and specifically of CD8+ (CD45RA+)CCR7+ and/or CD27+), CD4+ (CD45RA+CD31+), and CD4+ central memory T-cells (CD45RA(-)CCR7+). Interestingly, IL-7 in humans induced a preferential expansion of naïve T-cells, resulting in a broader T-cell repertoire than before the treatment; this effect was independent of age. This suggests that IL-7 therapy could enhance immune responses in patients with limited naïve T-cell numbers as in aged patients or after disease-induced or iatrogenic T-cell depletion. This overview highlights the role of IL-7 on T-cells in mice and humans.
ElKassar
Nahed
N
Experimental Immunology and Transplantation Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Gress
Ronald E
RE
D000818:Animals; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015851:Interleukin-7