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<SU-</SU CD8<SU-</SU thymocyte progenitor transition into double positive CD4<SU+</SU CD8<SU+</SU 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. Naive 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<SU+</SU and CD8<SU+</SU cells overall, and specifically of CD8<SU+</SU (CD45RA<SU+</SUCCR7<SU+</SU and/or CD27<SU+</SU), CD4<SU+</SU (CD45RA<SU+</SUCD31<SU+</SU), and CD4<SU+</SU central memory T-cells (CD45RA<SU-</SUCCR7<SU+</SU). Interestingly, IL-7 in humans induced a preferential expansion of naive 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 naive 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.</.