Early Macrophage and Mast Cell Responses in Diffuse Large B-Cell Lymphoma After Immunochemotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5206-5206
Author(s):  
Minna Taskinen ◽  
Anna Raunio ◽  
Maria Pöyhönen ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Sirpa Leppä
Keyword(s):  
Mast Cell ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5206 Background: The prognostic impact of tumor microenvironment on the survival of lymphoma patients has recently been reported. However, early molecular and cellular responses to immunochemotherapy are unknown. Here, we have compared the tumor-associated macrophage (TAM) and mast cell (MC) contents in the lymphoma tissue in vivo before and after the first immunochemotherapy course in a small cohort of aggressive B-cell lymphoma patients. Patients and methods: The population of this pilot study consisted of seven diffuse large B-cell lymphoma (DLBCL) and three grade IIIB follicular lymphoma (FL) patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). Paired tumor samples were collected before and a day after the first course of therapy, and evaluated immunohistochemically for CD68+, CD163+ macrophages and tryptase+ MCs. Freshly frozen lymphoma tissue containing enough material for paired mRNA analyses was available from 8 patients. Results: Comparing pre- and post-treatment tissue samples, an increase in the number of CD68+ TAMs was observed (p=0.023), whereas no variation in MC contents was found. If the patients were grouped according to response, i.e. remission (n=7) vs relapse (n=3), the most significant increase after therapy was observed in M2-type CD163+ TAM content (p=0.001). In the exon array analyses, the mRNA levels of both CD68 (p=0.052) and CD163 (p=0.023) genes increased after therapy. Conclusions: Our preliminary data suggest significant changes in macrophage content and their relative subsets in the lymphoma microenvironment after the first course of immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

Applicability of Different Immunohistochemistry Algorithms to Assess Gene Expression Profile In Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4134-4134
Author(s):  
Gonzalo Gutierrez-Garcia ◽  
Teresa Cardesa ◽  
Luis Colomo ◽  
Fina Climent ◽  
Santiago Mercadal ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 4134 Gene expression profile (GEP) allows to distinguish two groups with different origin in patients with diffuse large B-cell lymphoma (DLBCL): germinal-center (GC) and activated (ABC), with the latter having a significantly poorer outcome. However, GEP is a technique not available in current clinical practice. For this reason, attempts to reproduce GEP data by immunophenotyping algorithms have been made. The aim of this study was to apply the most popular algorithms in a series of patients with DLBCL homogeneously treated with immunochemotherapy, in order to assess the correlation with GEP data and their usefulness to predict response and outcome of the patients. One hundred fifty seven patients (80M/77F; median age 65 years) diagnosed with DLBCL in 5 institutions of the Grup per l'Estudi dels Limfomes de Catalunya I Balears (GELCAB) during a 5-year period, treated with Rituximab-containing regimens (in most cases, R-CHOP), in whom histological material to construct a tissue microarrays (TMA) was available, constituted the subjects of the present study. Four algorithms were applied: Colomo (Blood 2003, 101:78) using CD10, bcl-6 and MUM1/IRF4; Hans (Blood 2004, 103:275) using CD10, bcl-6 and MUM1/IRF4; Muris (J Pathol 2006, 208:714) using CD10 and MUM1/IRF4, and Choi (Clin Cancer Res 2009, 15:5494), using CD10, bcl-6, GCET1, FOXP1 and MUM1/IRF4. The thresholds used were those previously described. GEP studies were performed in 62 patients in whom fresh frozen material was available. Main clinical and evolutive data were recorded and analyzed. The proportion of positive cases for the different single antigens was as follows: CD10 26%, bcl-6 64%, GCET1 46%, FOXP1 78% and MUM1/IRF4 28%. The distribution of cases (GC vs. non-GC) according to the algorithms is detailed in the table. In 88 of 110 patients (80%) with all the antigens available, the patients were allocated in the same group (either GC or non-GC). When the immunochemistry was compared with GEP data, the sensitivity in the GC group was 59%, 52%, 70% and 40% for Colomo, Hans, Muris and Choi algorithms, respectively. The sensitivity in the non-GC group was 81%, 85%, 62% and 84%, respectively. On the other hand, the positive predictive value (PPV) in the GC group was 81%, 83%, 72% and 77%, respectively. In non-GC subset the PPV for the different algorithms was 59%, 55%, 72% and 52%, respectively. We observed a higher percentage of misclassified cases in the GC-phenotype subset than in the non-GC subgroup. None of the immunohistochemical algorithms showed a significant superiority as surrogate of GEP information among the others. The ability of GEP groups as well as of groups defined by the algorithms to predict complete response (CR) rate, progression-free survival (PFS) and overall survival (OS) of the patients is showed in the table. Thus, whereas the GEP groups showed significant prognostic value for CR rate, PFS and OS, none of the immunohistochemical algorithms were able to predict the outcome. In conclusion, in a homogeneous series of DLBCL patients treated with immunochemotherapy, the different immunohistochemical algorithms were not able to mimic the GEP information. The prognostic impact of the groups defined by immunohistochemistry (GC vs. non-GC) was particularly low. N (%) CR rate N (%) 5-year PFS (%) 5-year OS (%) Colomo algorithm GC 53 (44) 39 (74) 48 54 Non-GC 68 (56) 53 (78) 55 62 Hans algorithm GC 61 (41) 47 (77) 54 60 Non-GC 88 (59) 67 (76) 52 59 Muris algorithm GC 87 (57) 63 (72) 48 57 Non-GC 65 (43) 51 (78) 56 63 Choi algorithm GC 45 (33) 32 (71) 48 54 Non-GC 90 (67) 70 (78) 52 61 Gene expression profile 30 (58) 25 (83) 76* 80** GC Activated 22 (42) 17 (77) 31* 45** * p=0.005, ** p=0.03. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Six Versus Eight Cycles of Standard Regimen in Patients With Diffuse Large B-Cell Lymphoma

2020 ◽  
Author(s):  
Kana Oiwa ◽  
Kei Fujita ◽  
Shin Lee ◽  
Tetsuji Morishita ◽  
Hikaru Tsukasaki ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Standard Regimen ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals B-cell–specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice

Blood ◽  
2016 ◽  
Vol 127 (22) ◽  
pp. 2732-2741 ◽  
Author(s):  
Gero Knittel ◽  
Paul Liedgens ◽  
Darya Korovkina ◽  
Jens M. Seeger ◽  
Yussor Al-Baldawi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Specific Expression ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Conditional Expression ◽  
Large B Cell

Key Points B-cell–specific expression of Myd88p.L252P leads to the development of DLBCL in mice. The Myd88p.L252P mutation cooperates with BCL2 amplifications in ABC-DLBCL lymphomagenesis in vivo.

scholarly journals Prognostic impact of protein kinase C β II expression in R-CHOP-treated diffuse large B-cell lymphoma patients

2010 ◽  
Vol 23 (5) ◽  
pp. 686-693 ◽  
Author(s):  
Sari Riihijärvi ◽  
Satu Koivula ◽  
Heidi Nyman ◽  
Karin Rydström ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Kinase C ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era

2009 ◽  
Vol 100 (10) ◽  
pp. 1842-1847 ◽  
Author(s):  
Ritsuko Seki ◽  
Koichi Ohshima ◽  
Tomoaki Fujisaki ◽  
Naokuni Uike ◽  
Fumio Kawano ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells

2020 ◽  
Vol 52 (4) ◽  
pp. 401-410
Author(s):  
Mengyu Xi ◽  
Wan He ◽  
Bo Li ◽  
Jinfeng Zhou ◽  
Zhijian Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Anticancer Activities ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common category and disease entity of non-Hodgkin lymphoma. Osalmide and pterostilbene are natural products with anticancer activities via different mechanism. In this study, using a new synthetic strategy for the two natural products, we obtained the compound DCZ0801, which was previously found to have anti-multiple myeloma activity. We performed both in vitro and in vivo assays to investigate its bioactivity and explore its underlying mechanism against DLBCL cells. The results showed that DCZ0801 treatment gave rise to a dose- and time-dependent inhibition of cell viability as determined by CCK-8 assay and flow cytometry assay. Western blot analysis results showed that the expression of caspase-3, caspase-8, caspase-9 and Bax was increased, while BCL-2 and BCL-XL levels were decreased, which suggested that DCZ0801 inhibited cell proliferation and promoted intrinsic apoptosis. In addition, DCZ0801 induced G0/G1 phase arrest by downregulating the protein expression levels of CDK4, CDK6 and cyclin D1. Furthermore, DCZ0801 exerted an anti-tumor effect by down-regulating the expressions of p-PI3K and p-AKT. There also existed a trend that the expression of p-JNK and p-P38 was restrained. Intraperitoneal injection of DCZ0801 suppressed tumor development in xenograft mouse models. The preliminary metabolic study showed that DCZ0801 displayed a rapid metabolism within 30 min. These results demonstrated that DCZ0801 may be a new potential anti-DLBCL agent in DLBCL therapy.

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