In vivo, rAGR2 accelerated tumor growth in melanoma and lung cancer models, accompanied by increased TAM accumulation, a shift toward M2 polarization, and suppressed T-cell function.<h4>Discussion</h4>AGR2 drives tumor progression by reprogramming TAMs toward an M2 phenotype and attenuating T-cell function via the CD98hc-xCT/p-ERK pathway, highlighting its potential as both a prognostic marker and a therapeutic target. The gene discussed is SLC3A2; the disease is melanoma.