TP53mut confers immunochemotherapy resistance and poor clinical outcome of DLBCL patients.1,6–8 As an alternative mechanism of lymphoma progression, TP53mut alters host innate and adaptive immune responses,9 thus contributing to immunosuppressive TME, with decreasing CD4+T and CD8+T cell components.8,9 To our knowledge, this is the first report to identify ERVs as TP53mut-downstream targets in DLBCL, whose inhibition depended on a histone-methylation manner, resulting from increased SUV39H1 expression and H3K9 methylation. Here, CD4 is linked to lymphoma.