Lymphoma B cell-mediated immune synapse in Richter syndrome. This figure focuses on mechanism of tumoral escape in the germinal center of lymph nodes. PD-1 delivers inhibitory signals to TLs after binding with its ligands PD-L1 or PD-L2, on the surface of malignant B lymphocytes, in the tumor microenvironment. Behdad et al. (99). hypothesize that in RS, tumoral B lymphocytes share characteristics with Bregs: i) expression of co-inhibitory ligands such as PD-L1/PD-L2, allowing TL exhaustion, ii) the ability to induce FOXP3+ Treg expansion, and iii) the ability to recruit Myeloid-Derived Suppressor Cell (MDSC) or monocytes/macrophages (TAMs). Malignant B-cells can also directly express a variety of suppressive ligands and cytokines: i) TGF-β to promote Treg development and inhibit the differentiation of CD4+ TLs into Th1 or Th17 lymphocytes, and ii) IL-10 to promote CD4+ CD25+ FOXP3+ Treg development and Fas-L production (particularly for CD5+ B lymphocytes), leading to cell death in vitro. Bregs, Regulatory B Lymphocytes; IL-10, Interleukine 10; IFNγ, Interferon Gamma; MDSC, Myeloid-Derived Suppressor Cell; MHC, Major Histocompatibility Complex; PD-1, Programmed Death 1; PD-L1, Programmed Death Ligand 1; PD-L2, Programmed Death Ligand 2; RS-DLBCL, Richter Syndrome, Diffuse Large B-Cell Lymphoma subtype; TAM, Tumor Associated Macrophage; TCR, T-cell Receptor; TGF-β, Transforming Growth Factor Beta; TL, T Lymphocyte; Tregs, Regulatory T Lymphocytes.