Tumor immune evasion and the Let-7 family: insights into mechanisms and therapies.

Tumor immune evasion is a complex and adaptive mechanism that allows cancer cells to escape immune detection and destruction, contributing to malignancy progression and poor therapeutic outcomes. This review article explores the integral role of the let-7 family of microRNAs (miRNAs) in mediating tumor immune evasion, particularly how these regulators influence the tumor microenvironment (TME) and immune cell functionality. The let-7 family, known for its tumor-suppressive roles, modulates key immune checkpoints, including PD-L1, and pathways linked to immune response regulation, such as the STAT3/SOCS axis, impacts macrophage polarization and modulates immune cell function. Dysregulation of let-7 miRNAs can enhance tumor immune evasion through mechanisms such as downregulating major histocompatibility complex (MHC) expressions, promoting immunosuppressive cell populations, and manipulating metabolic pathways, which together establish an immunosuppressive TME. Conversely, specific let-7 members show potential in restoring anti-tumor immunity by reversing immune suppression and improving T cell responses. By synthesizing current research, this article underscores the dual role of let-7 in both promoting and inhibiting tumor immune evasion, suggesting their potential as therapeutic targets and biomarkers in cancer immunotherapy. Future studies on the context-dependent roles and advanced delivery systems for let-7-targeting therapies are crucial for enhancing immunotherapeutic efficacy and improving patient outcomes across malignancies.