A study uncovered an RNA‑guided mechanism by which STAT3 signaling modulates CD4+ T helper cell differentiation within non‑small cell lung cancer (NSCLC), altering epigenetic and epitranscriptomic states. The team demonstrated that manipulating RNA‑dependent STAT3 activity shifts tumor‑infiltrating T cell programs, with implications for enhancing immunotherapy responsiveness. The authors present mechanistic data and propose RNA‑guided STAT3 modulation as a targetable axis to reprogram the tumor immune microenvironment. For readers: epitranscriptomics refers to chemical modifications on RNA that affect function without changing sequence.