Prognostic implications of tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B‐cell lymphoma in the North Indian population

Apmis ◽  
2021 ◽  
Author(s):  
Mayur Parkhi ◽  
Debajyoti Chatterjee ◽  
Amanjit Bal ◽  
Poorva Vias ◽  
Budhi Singh Yadav ◽  
...  
Keyword(s):  
Indian Population ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Microenvironment ◽  
The North ◽  
Large B Cell Lymphoma ◽  
Checkpoint Pathway ◽  
Tumor Immune Microenvironment ◽  
Prognostic Implications ◽  
Large B Cell

scholarly journals Tumor Immune Microenvironment Components and Checkpoint Molecules in Anaplastic Variant of Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianqi Xu ◽  
Jia Chai ◽  
Kaijing Wang ◽  
Qingge Jia ◽  
Yixiong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Clinicopathological Features ◽  
Immune Microenvironment ◽  
Large B Cell Lymphoma ◽  
Tumor Immune Microenvironment ◽  
Large B Cell

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.

scholarly journals Helicobacter pylori infection disturbs the tumor immune microenvironment and is associated with a discrepant prognosis in gastric de novo diffuse large B-cell lymphoma

2021 ◽  
Vol 9 (10) ◽  
pp. e002947
Author(s):  
Yuwei Deng ◽  
Wenjia Su ◽  
Junwen Zhu ◽  
Hongfei Ji ◽  
Xiaoping Zhou ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Microenvironment ◽  
Large B Cell Lymphoma ◽  
Tumor Immune Microenvironment ◽  
H Pylori ◽  
Large B Cell

BackgroundGastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL.MethodsA retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed.ResultsThe median follow-up of the 252 patients was 66.6 months (range 0.7–119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H. pylori-positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p<0.001) and OS (89.2% vs 76.6%, p<0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival.ConclusionH. pylori-evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.

scholarly journals PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications

Oncotarget ◽  
2016 ◽  
Vol 7 (37) ◽  
pp. 59976-59986 ◽  
Author(s):  
Wei Xing ◽  
Karen Dresser ◽  
Rui Zhang ◽  
Andrew M. Evens ◽  
Hongbo Yu ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinicopathologic Features ◽  
Large B Cell Lymphoma ◽  
Prognostic Implications ◽  
Large B Cell

Exploring the Immune Microenvironment of Diffuse Large B Cell Lymphoma in a Tissue Microarray: Predicting Survival with a Score That Incorporates Macrophages, Cytotoxic and Regulatory T Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 951-951 ◽  
Author(s):  
Rita Coutinho ◽  
Andrew James Clear ◽  
David Andrew Owen ◽  
Paul Greaves ◽  
Simon L. Hallam ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Single Centre ◽  
Immune Microenvironment ◽  
Prognostic Information ◽  
Large B Cell Lymphoma ◽  
Prognostic Groups ◽  
Large B Cell

Abstract Abstract 951 Gene expression profiling studies in Diffuse Large B cell Lymphoma (DLBCL) have described signatures enriched in genes representing the immune microenvironment. These signatures, together with the cell of origin classification have prognostic significance. However, a comprehensive functional understanding of the role of inflammation and the immune response in DLBCL is still lacking. The use of immunohistochemistry (IHC) to validate and elaborate upon molecular results is appealing. Our objective was to assess the cellular composition of the non-malignant population in DLBCL quantitatively and thoroughly in a single centre TMA of patients with DLBCL with corresponding clinical and survival data. Based on reported findings and known functional interactions a panel of antibodies were selected that included CD68, FOXP3 and TIA-1. IHC was performed on TMAs from high quality formalin-fixed paraffin-embedded diagnostic tissue biopsies of DLBCL from 1977 to 2009. Triplicate cores were made from areas of representative tumour tissue, arrayed onto glass slides and stained for a panel of antibodies, aiming to characterize immune cell subsets. The TMA included tissue from 218 patients: 128 males, 90 females, with a median age of 55 (18-94) years; 23.2% high-int/high risk IPI; with median follow up of 3,1 years. 33% of patients were treated in the rituximab era. Absolute numbers of positive cells were counted across all intact cores using an automated image analysis system (Ariol), confirmed by histopathologists, and means calculated and corrected to a 1 mm2 area. A training-validation set method was used to generate optimal cutoff values discriminating prognostic groups and comparisons performed using the chi-square test. Among nine antibodies examined, statistically significant prognostic information was provided using staining for FOXP3, TIA-1 and CD68. Using single cut-offs of positive cells/mm2 to define low and high marker density, two prognostic groups were defined for each marker. Patients with a more favourable prognosis had the highest cell density for FOXP3, TIA-1 and CD68. To clarify whether there was an additive prognostic relationship we developed a score that incorporated these three markers. This scoring system allowed us to discriminate two subgroups of patients with divergent survival parameters (fig 1).Marker (cutoff value high vs low)Overall Survival at 3yr (high vs low)Progression Free Survival at 3yr (high vs low)Disease Specific Survival at 3yr (high vs low)FOXP3 (450+ cells/mm2)64% vs 44% (p 0.005)55% vs 36% (p 0.001)69% vs 54% (0.01)CD68 (900+ cells/mm2)58% vs 28% (p 0.023)50% vs 20% (p 0.05)66% vs 36% (p 0.005)TIA-1 (2500+ cells/mm2)76% vs 45% (p 0.002)66% vs 41% (p 0.01)80% vs 56% (p 0.005)Combined Score68% vs 39% (p 0.0002)60% vs 32% (p 0.0003)73% vs 49% (p 0.0008) A Cox regression model was developed, incorporating age, IPI, rituximab treatment and IHC score. The score results were validated as independent prognostic markers for OS, PFS and DSS, together with age, IPI (for OS and DSS) and rituximab (for PFS). We confirm that there is heterogeneity in immune cell infiltration at diagnosis in DLBCL, and we provide correlative prognostic data to suggest a corresponding biological relevance. Attributing single cut-off values for immune cell markers is feasible, attractive as a clinical tool, and appears to provide robust prognostic information. In our single centre cohort we found that higher numbers of macrophages, Tregs and cytotoxic T cells correlate independently with improved patient survival. CD68 has been associated with an adverse prognosis in lymphoid malignancies but phenotypic diversity of macrophages may account for this study's finding and will be explored using macrophage subset specific markers. Our multivariate analysis revealed that the IHC results have an independent impact on survival on this cohort of DLBCL patients. We are currently validating this approach in an independent TMA of R-CHOP treated patients. Combining these three different immune cell parameters allowed us to discriminate prognostic subgroups providing further evidence of the impact of the non-malignant immune cells in the biology of DLBCL and validating their role as potential therapeutic targets for intervention. Disclosures: Gribben: Gilead: Honoraria; Mundipharma: Honoraria; GSK: Honoraria; Celgene: Honoraria; Roche: Honoraria; Pharmacyclics: Honoraria.

scholarly journals Prognostic implications of 5-hydroxymethylcytosines from circulating cell-free DNA in diffuse large B-cell lymphoma

2019 ◽  
Vol 3 (19) ◽  
pp. 2790-2799 ◽  
Author(s):  
Brian C.-H. Chiu ◽  
Zhou Zhang ◽  
Qiancheng You ◽  
Chang Zeng ◽  
Elizabeth Stepniak ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Free Dna ◽  
Large B Cell Lymphoma ◽  
Genome Wide ◽  
Key Points ◽  
Prognostic Implications ◽  
Large B Cell

Key Points Genome-wide 5hmC loci can be profiled in 1 to 2 ng of cfDNA from blood plasma and correlate with clinical features of DLBCL. 5hmC in cfDNA collected at the time of DLBCL diagnosis is associated with EFS and OS, independent of established prognostic factors.

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