Figure 1.
Tumor microenvironment in Hodgkin lymphoma and other B-cell lymphomas. (A) Histology and morphological characteristics of TME of cHL, MGZL, PMLBCL, DLBCL not otherwise specified and FL. Histology images (top row) showing the different subtypes of lymphomas and the corresponding drawings (second row) showing the cell types in their TMEs. As shown in the drawings, the TME in cHL demonstrates variable cellularity, which is different in each subtype. In mixed cellularity cHL, the TME consists of a polymorphous reactive infiltrate of B and T cells, neutrophils, histiocytes, plasma cells, and mast cells. In NScHL, the TME is specifically characterized by fibroblast-like cells and sclerosis. In MGZL, the TME typically comprises histiocytes, irregular sclerosis, and necrosis. In PMLBCL, the TME is variable but usually consists of histiocytes, lymphocytes, and compartmentalizing fibrosis. In DLBCL not otherwise specified (NOS), the TME is diminished but is quite variable; In FLs, the TME is partly similar to that of cHL, although in FL, it is rich in follicular dendritic cells. (third row) the cell types shown in the drawings, and (bottom row) the keys of the cell types. (B) The composite figure shows CD20 and CD3 immunostaining in 2 specific DLBCLs, PMLBCL and T-cell/histiocyte-rich B-cell lymphoma, and FL. In all of these lymphomas, tumor cells are immunostained for CD20, whereas their TME contains reactive infiltrates rich in CD3+ T cells. Topological and quantitative analyses of microenvironmental cells interacting with tumor cells were performed using an unsupervised clustering analysis of the TME. This analysis revealed that the TME in THRLBCL is distinct from cHL and DLBCL NOS with respect to PD-1/PD-L1 expression and spatial organization (spatial immune signature).24 In FLs and DLBCL NOS, which are often resistant to anti–PD-1 therapy,25,26 PD-L1 copy gains are not observed.27,28 It has been speculated that the lower incidence of tumor cell-specific PD-L1 expression in FL and DLBCL NOS, when compared with that in cHL, is compensated for by the higher density of PD-L1+ TAMs to ensure adequate PD-1 engagement for immune evasion.24 Original magnification ×10 (NScHL, FL), ×20 (PMLBCL, DLBCL NOS), and ×40 (MCcHL, GZL) (A) and ×20 (B).

Tumor microenvironment in Hodgkin lymphoma and other B-cell lymphomas. (A) Histology and morphological characteristics of TME of cHL, MGZL, PMLBCL, DLBCL not otherwise specified and FL. Histology images (top row) showing the different subtypes of lymphomas and the corresponding drawings (second row) showing the cell types in their TMEs. As shown in the drawings, the TME in cHL demonstrates variable cellularity, which is different in each subtype. In mixed cellularity cHL, the TME consists of a polymorphous reactive infiltrate of B and T cells, neutrophils, histiocytes, plasma cells, and mast cells. In NScHL, the TME is specifically characterized by fibroblast-like cells and sclerosis. In MGZL, the TME typically comprises histiocytes, irregular sclerosis, and necrosis. In PMLBCL, the TME is variable but usually consists of histiocytes, lymphocytes, and compartmentalizing fibrosis. In DLBCL not otherwise specified (NOS), the TME is diminished but is quite variable; In FLs, the TME is partly similar to that of cHL, although in FL, it is rich in follicular dendritic cells. (third row) the cell types shown in the drawings, and (bottom row) the keys of the cell types. (B) The composite figure shows CD20 and CD3 immunostaining in 2 specific DLBCLs, PMLBCL and T-cell/histiocyte-rich B-cell lymphoma, and FL. In all of these lymphomas, tumor cells are immunostained for CD20, whereas their TME contains reactive infiltrates rich in CD3+ T cells. Topological and quantitative analyses of microenvironmental cells interacting with tumor cells were performed using an unsupervised clustering analysis of the TME. This analysis revealed that the TME in THRLBCL is distinct from cHL and DLBCL NOS with respect to PD-1/PD-L1 expression and spatial organization (spatial immune signature).24 In FLs and DLBCL NOS, which are often resistant to anti–PD-1 therapy,25,26 PD-L1 copy gains are not observed.27,28 It has been speculated that the lower incidence of tumor cell-specific PD-L1 expression in FL and DLBCL NOS, when compared with that in cHL, is compensated for by the higher density of PD-L1+ TAMs to ensure adequate PD-1 engagement for immune evasion.24 Original magnification ×10 (NScHL, FL), ×20 (PMLBCL, DLBCL NOS), and ×40 (MCcHL, GZL) (A) and ×20 (B).

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