Mechanism Study of the Effect of GSPT1 Inhibitor MRT-2359 on Immune Escape in Non-Small Cell Lung Cancer

This study is dedicated to investigating the effects of the GSPT1 inhibitor MRT-2359 on the functional modulation of immune cells in the context of non-small cell lung carcinoma and to elucidate the underlying mechanisms. Accumulating evidence has highlighted the aberrant upregulation of eRF3a/GSPT1 across a spectrum of malignancies, positioning GSPT1 as a highly promising target for therapeutic intervention. Our findings demonstrate that MRT-2359 efficaciously induces the degradation of GSPT1 within NSCLC cells. Utilizing RNA sequencing (RNA-seq) and other advanced molecular techniques, we have postulated that MRT-2359 modulates the expression of CD276, thereby suppressing the tumor immune evasion phenotype of NSCLC cells. In vivo studies corroborate the tumor-suppressive effects of MRT-2359 in murine models, with immunohistochemical analyses revealing a significant reduction in GSPT1 and CD276 within tumor tissues. Concurrently, an enhanced infiltration of granzyme B (GZMB)-positive cells was observed. These collective findings provide reference value for MRT-2359 advancement towards clinical application.