CD27 in MCLs. (A) Representative histological sections with strong, moderate, and negative CD27 IHC staining in SOX11⁺ nodal MCL primary sample. (B-C) Mean gray value (MGV) quantification of CD27 staining (see supplemental Methods) in SOX11⁺ (n = 40) and SOX11⁻ (n = 11) nodal MCLs (B) and in cases with low and high CD70 expression (C). The significance difference was determined by independent samples Student t test: n.s., not significant. (D) Immune evasion mechanism model of SOX11/CD70/T_reg cells axis in nodal MCLs. Our results show that SOX11 binds to a regulatory region of CD70. CD40L present in nodal MCL niches, probably in macrophages (Mф) and/or activated T cells, induces the expression of CD70 in SOX11-expressing MCL cells. The association of CD70 expression with blastoid/pleomorphic variants and high proliferation suggest that other factors may also influence CD70 expression in MCLs. CD70 favors tumor cell survival and proliferation, as well as the infiltration and/or induction of effector T_reg (eT_reg) cells, probably through the activation of the CD27/CD70 signaling pathway. SOX11-mediated CD70 expression in MCLs could promote apoptosis, anergy, or exhaustion of T cells, reducing the number of activated/effector T cells (eTC), in nodal MCL TMEs. At the same time, increased T_reg cells could impair the infiltration of eTC and inhibit the cytotoxicity of effector immune cells (CCs). CD70/T_reg cells immune evasion mechanism could favor tumor cell survival, drug resistance, and relapse, frequently seen in MCL.