Manipulating the tumor immune microenvironment to improve cancer immunotherapy: IGF1R, a promising target

Abstract

Cancer immunotherapy has made impressive advances in improving the outcome of patients affected by malignant diseases. Nonetheless, some limitations still need to be tackled to more efficiently and safely treat patients, in particular for those affected by solid tumors. One of the limitations is related to the immunosuppressive tumor microenvironment (TME), which impairs anti-tumor immunity. Efforts to identify targets able to turn the TME into a milieu more auspicious to current immuno-oncotherapy is a real challenge due to the high redundancy of the mechanisms involved. However, the insulin-like growth factor 1 receptor (IGF1R), an attractive drug target for cancer therapy, is emerging as an important immunomodulator and regulator of key immune cell functions. Here, after briefly summarizing the IGF1R signaling pathway in cancer, we review its role in regulating immune cells function and activity, and discuss IGF1R as a promising target to improve anti-cancer immunotherapy.

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)

“…Findings from our study were consistent with those in previous studies and further revealed that miR-30a-3p, acting as a tumor suppressor, was directly sponged and downregulated by circ_PPAPDC1A, with upregulation of IGF1R and activation of IGF1R/PI3K/ AKT/mTOR signaling. However, there are also study [ 41 ] indicates that LINC01436 promotes NSCLC progression by functioning as a miR-30a-3p sponge to regulate the expression of its target gene EPAS1.However, our study indicates that there is no significant difference in the expression of EPAS1 in Osimertinib resistance cells and it has no significant impact on the sensitivity to Osimertinib. So, we believe that EPAS1 may be involved in the occurrence of NSCLC through miR-30a-3p, but its impact on Osimertinib resistance is minimal.…”

“…Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine-protein kinase (TPK) receptor that primarily binds with the ligand insulin-like growth factor-1 (IGF-1). This binding trigger conformational changes and autophosphorylation of specific tyrosine residues, initiating signal transduction pathways that play a crucial role in cell proliferation, adhesion, transformation, and apoptosis [ 41 ]. Current research [ 42 ] indicates that IGF-1R is highly expressed in various tumors and functions as an oncogene in the development and progression of cancer.…”

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

“…In the field of oncology, the insulin-like growth factor 1/insulin-like growth factor 1 receptor (IGF1/IGF1R) axis stands out as one of the most extensively studied pathways [8,9]. From a molecular point of view, IGF1 binds to IGF1R, triggering its intracellular kinase activity.…”