TY  - JOUR
T1  - Mechanistic Insights into miR-23a/27a/24-2 Cluster-Mediated Tumor Immune Evasion and Resistance to Immune Checkpoint Blockade in Non-Small Cell Lung Cancer
A1  - Pieter Botha
A1  - Anel Van Wyk
A1  - Johan Marais
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2026
VL  - 6
IS  - 1
DO  - 10.51847/PZ3cesSrWh
SP  - 1
EP  - 20
N2  - Programmed death-ligand 1 (PD-L1) and major histocompatibility complex class I (MHC-I) play central roles in enabling tumors to evade immune surveillance and in conferring resistance to PD-1/PD-L1 inhibitors. The present work demonstrates that increased expression of all members of the miR-23a/27a/24−2 cluster is associated with reduced patient survival, heightened immune escape, and diminished responsiveness to PD-1/PD-L1 blockade in individuals with non-small cell lung cancer (NSCLC). Forced expression of these cluster miRNAs promoted PD-L1 production through direct suppression of Cbl proto-oncogene B (CBLB). It concurrently lowered MHC-I levels by elevating eukaryotic initiation factor 3B (eIF3B) via inhibition of microphthalmia-associated transcription factor (MITF). We further established that sustained expression of the miR-23a/27a/24−2 cluster in NSCLC cells is supported by augmented Wnt/β-catenin pathway activity, which strengthens the binding of transcription factor 4 (TCF4) to the cluster’s promoter region. Pharmacological interference with eIF3B signaling markedly improved the efficacy of PD-1/PD-L1 blockade therapy, particularly in NSCLC tumors with high levels of the miR-23a/27a/24−2 cluster. This improvement resulted from restored MHC-I surface expression while preserving the elevated PD-L1 induced by the miRNA cluster. Overall, this study clarifies the self-reinforcing loop that maintains miR-23a/27a/24−2 cluster activity and reveals the detailed molecular processes through which these miRNAs drive immune evasion and therapeutic resistance. These insights also identify a targeted intervention strategy for managing NSCLC cases characterized by strong expression of the miR-23a/27a/24−2 cluster.
UR  - https://smerpub.com/article/mechanistic-insights-into-mir-23a27a24-2-cluster-mediated-tumor-immune-evasion-and-resistance-to-i-soqihfe0ddqbhis
ER  -