Abstract
BackgroundAnaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear.MethodsThirty A-DLBCL patients were enrolled to study tumor immune microenvironment components and checkpoint molecules and their associations with clinicopathological features and prognosis.ResultsPatients with A-DLBCL presented higher expression of PD-L1 (40% vs 10%, P=0.004) than patients with ordinary DLBCL. FISH analysis showed that extra copies of PD-L1 were more frequent in A-DLBCL cases than in ordinary DLBCL cases (23.3% vs 4.0%, P=0.001). The numbers of PD-1+ TILs (tumor infiltrating lymphocytes) and CD8+T cells were significantly lower in A-DLBCL versus ordinary DLBCL. In contrast, the numbers of GATA3+ Th2 cells, FOXP3+ Tregs and CD33+ myeloid-derived suppressor cells (MDSCs) were significantly higher in A-DLBCL than in ordinary DLBCL. The associations between clinicopathological features and tumor immune microenvironment cell frequency were analyzed in A-DLBCL patients. Briefly, the number of PD-1+ TILs was lower and the number of CD33+ MDSCs was higher in patients with mutated TP53 compared to those with wild-type TP53. The number of FOXP3+ Tregs was much lower in patients with a noncomplete response (CR) to chemotherapy than in those with a complete response. The number of CD8+ T cells showed a decreasing trend in patients with high International Prognostic Index (IPI) scores and in those with concurrent MYC and BCL2 and/or BCL6 abnormalities. Univariate survival analysis showed that patients with PD-L1+, mPD-L1+(PD-L1+ nonmalignant stromal cells) or mPD-L1+ status had a significantly poorer overall survival (OS) than those with PD-L1- status. An increase in the number of CD3+ T cells, FOXP3+ Treg cells and T-bet+ Th1 cells was significantly associated with prolonged OS in patients with A-DLBCL.ConclusionOur study suggests that A-DLBCL displays a distinct pattern of tumor immune microenvironment components and checkpoint molecules that distinguish it from ordinary DLBCL. The analysis of tumor immune microenvironment components and checkpoint molecules could help in predicting the prognosis of A-DLBCL patients and determining therapeutic strategies targeting the tumor immune microenvironment.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma; it is more prevalent in elderly patients, with a median age in the 70s
myeloid-derived suppressor cells (MDSCs) and Tumor-associated Macrophages We found that MDSCs were more abundant in A-DLBCL than in ordinary DLBCL(P=0.039), with 33.8 ± 4.2/high-power fields (HPFs) vs 20.6 ± 4.1/ HPF, represented by CD33, while M2 tumor-associated macrophage (TAM) (CD163) and M1/ M2 TAMs (CD68) showed no significant difference between ADLBCL and ordinary DLBCL
As we observed a significantly reduced quantity of PD-1+ tumor-infiltrating lymphocytes (TILs), an increased quantity of CD33+ cells, and a high possibility of non-CR to treatment related to a low quantity of FOXP3+ cells in our study, we propose that the prognosis of A-DLBCL is poorer than that of ordinary DLBCL
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma; it is more prevalent in elderly patients, with a median age in the 70s. DLBCL cases can be subdivided into morphologic variants, molecular and immunophenotypical subgroups, and distinct disease entities. Anaplastic variant of diffuse large B-cell lymphoma(ADLBCL) is a rare morphological type, representing approximately 3-4% of all DLBCL cases [1, 2], that is characterized by large or very large, pleomorphic or bizarreshaped lymphoma cells. In our study on 3 cases of primary CNS ADLBCL, patients had MYC/BCL2 co-expression, and concurrent MYC and BCL2 and/or BCL6 genetic abnormalities, and constitutive NF-kB pathway activation [4]. Our results suggest that A-DLBCL displays many genetic alterations and biological features that differ greatly from ordinary DLBCL. Anaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. The status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear
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