In stiff matrices, tumor cells secrete more CSF-1, which promotes the accumulation of M2 macrophages.486,487 Viral infections can also influence TAM polarization; Epstein-Barr Virus (EBV) induces M2 polarization in nasopharyngeal carcinoma by producing Ataxia Telangiectasia and Rad3-related protein (ATR), which supports tumor progression.488 Other cells within the TME also contribute to the M2 phenotype transition of TAMs. The gene discussed is ATR; the disease is viral infectious disease.