Prognostic Impact of Tumor Infiltrating FOXP3 Positive Regulatory T Cells in Diffuse Large B-Cell Lymphoma at Diagnosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1565-1565
Author(s):  
Jae-Yong Kwak ◽  
Na-Ri Lee ◽  
Eun-Kee Song ◽  
Kyu Yun Jang ◽  
Ha Na Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Tumor infiltrating immune cells play an important role in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In the present study, we have identified a subset of tumor infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens and evaluated its prognostic significance. Ninety-six patients with DLBCL were retrospectively evaluated. Expression pattern of FOXP3 protein was examined using standard immunohistochemistry in paraffin-embedded tissue samples. The median overall survival (OS) was 28 months. Compared to the others, the patients with higher percentage of FOXP3-positive Tregs in the initial tumor biopsy, showed a significantly longer OS (p=0.003). When prognostic factors were evaluated in a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were shown to be independent predictors of OS. In conclusion, the presence of increased percentage of FOXP3-positive Tregs in DLBCL predicts a better prognosis. Figure Figure

scholarly journals Clinical Features and Prognostic Significance of NOTCH1 Mutations in Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhongqi Li ◽  
Fang Yu ◽  
Wenle Ye ◽  
Liping Mao ◽  
Jiansong Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of large lymphoid B cell malignancy with distinct clinical and genetic features. Recently, NOTCH1 mutations were identified in DLBCL cases by Next-generation sequencing (NGS), but the clinical features and prognostic impact were not systematically studied. Here, NOTCH1 genes in 161 DLBCL samples were sequenced by NGS. The prognostic value of NOTCH1 mutations was assessed in the context of clinical and laboratory factors, such as international prognostic index (IPI), cell-of-origin classification, double expression of BCL2 and c-MYC. The combined data from three Western cohorts were used to validate these results. As a result, NOTCH1 mutations were found in 17(10.6%) patients, and three patients had a hotspot mutation of c.7541_7542delCT. The presence of NOTCH1 mutations was significantly associated with poor complete response and progression free survival(PFS), which was independent of established clinical and laboratory parameters. In addition, 30 (1.92%) of 1562 patients treated with R-CHOP regimen in those combined Western cohorts had NOTCH1 mutations. Meta-analysis of the Western cohorts confirmed that NOTCH1 mutations were also associated with poor PFS and OS. In conclusion, DLBCL patients with the NOTCH1 mutations have worse PFS and OS, and the NOTCH1 mutations can be used as an independent predictor for patients with DLBCL.

Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis

2008 ◽  
Vol 49 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Na-Ri Lee ◽  
Eun-Kee Song ◽  
Kyu Yun Jang ◽  
Ha Na Choi ◽  
Woo Sung Moon ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Adverse prognostic impact of regulatory T‐cells in testicular diffuse large B‐cell lymphoma

2020 ◽  
Vol 105 (6) ◽  
pp. 712-721
Author(s):  
Marjukka Pollari ◽  
Teijo Pellinen ◽  
Marja‐Liisa Karjalainen‐Lindsberg ◽  
Pirkko‐Liisa Kellokumpu‐Lehtinen ◽  
Suvi‐Katri Leivonen ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals An NCCN-IPI based immune-related gene prognostic model for diffuse large B-cell lymphoma

2021 ◽  
Author(s):  
Shidai Mu ◽  
Deyao Shi ◽  
Lisha Ai ◽  
Fengjuan Fan ◽  
Fei Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

AbstractBackgroundAn enhanced International Prognostic Index (NCCN-IPI) was built to better discriminate diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. However, there is an urgent need to identify novel valuable biomarkers in the context of targeted therapies, such as immune checkpoint blockade (ICB) therapy.MethodsGene expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. 73 immune-related hub genes in DLBCL patients with different IPI levels were identified by weighted gene co-expression network analysis (WGCNA), and 4 genes were selected to construct an IPI-based immune-related prognostic model (IPI-IPM). Afterward, the genetic, somatic mutational and molecular profiles of IPI-IPM subgroups were analyzed, as well as the potential clinical response of ICB in different IPI-IPM subgroups.ResultsThe IPI-IPM was constructed base on the expression of LCN2, CD5L, NLRP11 and SERPINB2, where high-risk patients had shorter overall survival (OS) than low-risk patients, consistent with the results in the GEO cohorts. The comprehensive results showed that a high IPI-IPM risk score was correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, high infiltration of CD8+ T cells and macrophages (M1, M2), as well as up-regulation of inhibitory immune checkpoints including PD-L1, LAG3 and BTLA, indicating more potential response to ICB therapy.ConclusionThe IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms on tumor progression and drug resistance, also sheds a light on developing immunotherapy for DLBCL.

Impact of Concordant and Discordant Bone Marrow Involvement on Outcome in Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2011 ◽  
Vol 29 (11) ◽  
pp. 1452-1457 ◽  
Author(s):  
Laurie H. Sehn ◽  
David W. Scott ◽  
Mukesh Chhanabhai ◽  
Brian Berry ◽  
Anna Ruskova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Bone Marrow Biopsies ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab. Patients and Methods We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies. Results In total, 795 patients were identified. Six hundred seventy (84.3%) of 795 had a negative bone marrow, 67 patients (8.4%) had concordant and 58 (7.3%) had discordant involvement. Median follow-up was 41 months (range, 1 to 115). Progression-free survival (PFS) was inferior in those with concordant (P < .001) and discordant (P = .019) involvement while overall survival (OS) was inferior in those with concordant involvement (P < .001) only. In a multivariate analysis controlling for the International Prognostic Index (IPI) score, concordant involvement remained an independent predictor of PFS (P < .001) and OS (P = .007). Discordant involvement was associated with older age, elevated lactate dehydrogenase, advanced stage, and increased number of extranodal sites and was not a negative prognostic factor independent of the IPI score. Conclusion The negative prognostic impact of discordant involvement is adequately represented by the IPI score, while the risk with concordant involvement is greater than that encompassed by this predictor. The results emphasize the need for accurate staging assessment of bone marrow involvement in DLBCL.

scholarly journals Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1967
Author(s):  
Pauli Vähämurto ◽  
Marjukka Pollari ◽  
Michael R. Clausen ◽  
Francesco d’Amore ◽  
Sirpa Leppä ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Increased Risk ◽  
Absolute Lymphocyte Counts ◽  
Large B Cell

Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267–3.086, p = 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175–0.757, p = 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.

scholarly journals High Levels of Regulatory T Cells in Blood Are a Poor Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma

2015 ◽  
Vol 144 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Chen Chang ◽  
Shang-Yin Wu ◽  
Yu-Wei Kang ◽  
Kun-Piao Lin ◽  
Tsai-Yun Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 945-951 ◽  
Author(s):  
Izidore S. Lossos ◽  
Carol D. Jones ◽  
Roger Warnke ◽  
Yasodha Natkunam ◽  
Herbert Kaizer ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Mrna Expression ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. BCL-6 is a proto-oncogene commonly implicated in DLBCL pathogenesis. A real-time reverse transcription–polymerase chain reaction assay was established for accurate and reproducible determination of BCL-6 mRNA expression. The method was applied to evaluate the prognostic significance ofBCL-6 expression in DLBCL. BCL-6 mRNA expression was assessed in tumor specimens obtained at the time of diagnosis from 22 patients with primary DLBCL. All patients were subsequently treated with anthracycline-based chemotherapy regimens. These patients could be divided into 2 DLBCL subgroups, one with high BCL-6 gene expression whose median overall survival (OS) time was 171 months and the other with low BCL-6 gene expression whose median OS was 24 months (P = .007). BCL-6 gene expression also predicted OS in an independent validation set of 39 patients with primary DLBCL (P = .01). BCL-6 protein expression, assessed by immunohistochemistry, also predicted longer OS in patients with DLBCL. BCL-6 gene expression was an independent survival predicting factor in multivariate analysis together with the elements of the International Prognostic Index (IPI) (P = .038). By contrast, the aggregate IPI score did not add further prognostic information to the patients' stratification byBCL-6 gene expression. High BCL-6 mRNA expression should be considered a new favorable prognostic factor in DLBCL and should be used in the stratification and the design of risk-adjusted therapies for patients with DLBCL.

scholarly journals The number of tumour-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+ regulatory T cells predicts outcome in diffuse large B-cell lymphoma

2007 ◽  
Vol 137 (4) ◽  
pp. 364-373 ◽  
Author(s):  
Sverker Hasselblom ◽  
Margret Sigurdadottir ◽  
Ulrika Hansson ◽  
Herman Nilsson-Ehle ◽  
Börje Ridell ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Cytotoxic T Cells ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium

Blood ◽  
2011 ◽  
Vol 117 (26) ◽  
pp. 7070-7078 ◽  
Author(s):  
Gilles Salles ◽  
Daphne de Jong ◽  
Wanling Xie ◽  
Andreas Rosenwald ◽  
Mukesh Chhanabhai ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cut Points ◽  
Large B Cell Lymphoma ◽  
Hla Dr ◽  
Large B Cell

The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.

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