Interleukin (IL)-7 Signaling in the Tumor Microenvironment

Interleukin (IL)-7 plays an important immunoregulatory role in different types of cells. Therefore, it attracts researcher's attention, but despite the fact, many aspects of its modulatory action, as well as other functionalities, are still poorly understood. The review summarizes current knowledge on the interleukin-7 and its signaling cascade in context of cancer development. Moreover, it provides a cancer-type focused description of the involvement of IL-7 in solid tumors, as well as hematological malignancies.The interleukin has been discovered as a growth factor crucial for the early lymphocyte development and supporting the growth of malignant cells in certain leukemias and lymphomas. Therefore, its targeting has been explored as a treatment modality in hematological malignancies, while the unique ability to expand lymphocyte populations selectively and without hyperinflammation has been used in experimental immunotherapies in patients with lymphopenia. Ever since the early research demonstrated a reduced growth of solid tumors in the presence of IL-7, the interleukin application in boosting up the anticancer immunity has been investigated. However, a growing body of evidence indicative of IL-7 upregulation in carcinomas, facilitating tumor growth and metastasis and aiding drug-resistance, is accumulating. It therefore becomes increasingly apparent that the response to the IL-7 stimulus strongly depends on cell type, their developmental stage, and microenvironmental context. The interleukin exerts its regulatory action mainly through phosphorylation events in JAK/STAT and PI3K/Akt pathways, while the significance of MAPK pathway seems to be limited to solid tumors. Given the unwavering interest in IL-7 application in immunotherapy, a better understanding of interleukin role, source in tumor microenvironment, and signaling pathways, as well as the identification of cells that are likely to respond should be a research priority.