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IFITM3 Identified as Key Modulator of Immunotherapy Response in Small Cell Lung Cancer

The WCLC presentation outlines a pathway that elevates tumor MHC‑I via NLRC5 to bolster CD8+ T cell attack.

Overview

  • Researchers from Shanghai Pulmonary Hospital and the University of Pittsburgh reported the findings at the 2025 World Conference on Lung Cancer.
  • Mechanistic studies show IFITM3 activates NLRC5 and promotes its nuclear translocation, increasing MHC‑I expression and antigen presentation.
  • Laboratory models demonstrated greater CD8+ T cell infiltration and cytotoxicity when IFITM3 was upregulated.
  • Across real‑world cohorts, IFITM3 expression correlated with MHC‑I levels and predicted improved progression‑free survival on chemoimmunotherapy.
  • Ethyl gallate induced IFITM3 and sensitized preclinical SCLC models to PD‑1 blockade, with clinical validation and safety testing still pending.