scholarly journals The microenvironment of DLBCL is characterized by non-canonical macrophages recruited by tumor-derived CCL5

2021 ◽  
Author(s):  
Benoît Manfroi ◽  
Maria De Grandis ◽  
Jerome Moreaux ◽  
Sebastien P Tabruyn ◽  
Jean-François Mayol ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Cells ◽  
Single Cell Analysis ◽  
B Cell Lymphoma ◽  
Gene Signature ◽  
Blood Monocytes ◽  
Tissue Invasion ◽  
Large B Cell Lymphoma ◽  
Survival Studies ◽  
Host Inflammatory Response

Tissue invasion by tumor cells induces a host inflammatory response variably impacting tumorigenesis. This has been well documented for tumor-associated macrophages (TAM) that could either play a pro/M2 or an anti/M1-tumoral function. TAM frequently infiltrate diffuse large B-cell lymphoma (DLBCL), an aggressive neoplasm arising from germinal center-experienced B cells. However, the pathway leading to TAM presence in DLBCL remains unknown and their impact unclear. Here, we show that some DLBCL tumor cells expressed the chemokine CCL5, enabling the differential recruitment of blood monocytes through their expression of CCR1 and CCR5. CCL5 expression by DLBCL was not related to molecular subtypes and healthy tonsillar B cells did not produce this chemokine, implying a post-transformation event. A single-cell analysis revealed that most DLBCL TAM had a non-canonical gene signature with the concomitant expression of M1 and M2 genes. The presence of non-canonical TAM may explain the absence of impact reported for macrophages on DLBCL development in some survival studies.

scholarly journals Long-Term Survival and Gradual Recovery of B Cells in Patients (Pts) with Refractory Large B Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel)

2021 ◽  
Vol 27 (3) ◽  
pp. S404-S405
Author(s):  
Caron A. Jacobson ◽  
Frederick L. Locke ◽  
Armin Ghobadi ◽  
David B. Miklos ◽  
Lazaros J. Lekakis ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization

2017 ◽  
Vol 10 (2) ◽  
pp. 508-514 ◽  
Author(s):  
Yukiko Nishi ◽  
Riko Kitazawa ◽  
Ryuma Haraguchi ◽  
Ayaka Ouchi ◽  
Yasuo Ueda ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Malignant Lymphoma ◽  
Cell Lymphoma ◽  
Clinical Phenotype ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Japanese Female ◽  
Old Japanese ◽  
Large B Cell

Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB) or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC) subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC) subtype.

Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4503-4506 ◽  
Author(s):  
Anja Mottok ◽  
Christoph Renné ◽  
Marc Seifert ◽  
Elsie Oppermann ◽  
Wolf Bechstein ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Rare Mutations ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Follicular Lymphomas ◽  
Large B Cell

Abstract STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.

scholarly journals Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

2021 ◽  
Vol 12 ◽  
Author(s):  
Erwan Dumontet ◽  
Stéphane J. C. Mancini ◽  
Karin Tarte
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Niche Adaptation ◽  
Functional Features

B-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches.

scholarly journals Inflammatory Cells in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2418
Author(s):  
Roberto Tamma ◽  
Girolamo Ranieri ◽  
Giuseppe Ingravallo ◽  
Tiziana Annese ◽  
Angela Oranger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

scholarly journals Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1350-1358 ◽  
Author(s):  
Ash A. Alizadeh ◽  
Andrew J. Gentles ◽  
Alvaro J. Alencar ◽  
Chih Long Liu ◽  
Holbrook E. Kohrt ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Single Gene ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractSeveral gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the “germinal center B cell–like” subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of “cell-of-origin” classification, “stromal signatures,” IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.

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