scholarly journals Integrated stress response and immune cell infiltration in an ibrutinib‐refractory mantle cell lymphoma patient following ONC 201 treatment

2018 ◽  
Vol 185 (1) ◽  
pp. 133-136 ◽  
Author(s):  
Jorge E. Romaguera ◽  
Hun J. Lee ◽  
Rohinton Tarapore ◽  
Varun Prabhu ◽  
Joshua Allen ◽  
...  
Keyword(s):  
Stress Response ◽  
Mantle Cell Lymphoma ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Integrated Stress Response ◽  
Lymphoma Patient ◽  
Mantle Cell ◽  
Mantle Cell Lymphoma Patient

A rare case of methotrexate and primaquine co‐administration in a mantle cell lymphoma patient

2019 ◽  
Vol 44 (5) ◽  
pp. 800-804 ◽  
Author(s):  
Alan L. Myers ◽  
Jitesh D. Kawedia ◽  
Ahmed Nader ◽  
Jason R. Westin ◽  
Brandon R. Shank
Keyword(s):  
Mantle Cell Lymphoma ◽  
Rare Case ◽  
Cell Lymphoma ◽  
Lymphoma Patient ◽  
Mantle Cell ◽  
Mantle Cell Lymphoma Patient

scholarly journals SOX11, CD70 and Treg cells configure the tumor immune microenvironment of aggressive mantle cell lymphoma

Blood ◽  
2021 ◽  
Author(s):  
Patricia Balsas ◽  
Luis Veloza ◽  
Guillem Clot ◽  
Marta Sureda-Gómez ◽  
Marta-Leonor Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
Mantle Cell Lymphoma ◽  
Tumor Cells ◽  
Treg Cell ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
Biological Behavior ◽  
Cell Infiltration ◽  
Mantle Cell ◽  
Sox11 Expression

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with a heterogeneous clinical and biological behavior. SOX11 oncogenic expression contributes to the aggressiveness of these tumors by different mechanisms including tumor and stromal cell interactions. However, the precise composition of the immune cell microenvironment of MCL, its possible relationship to SOX11 expression, and how it may contribute to tumor behavior is not well known. Here, we performed an integrative transcriptome analysis of 730 immune-related genes combined with the immune cell phenotype analysis by immunohistochemistry in SOX11+ and SOX11- primary nodal MCL cases and non-neoplastic reactive lymph nodes (RLN). SOX11+ MCL had a significant lower T-cell intratumoral infiltration compared to negative cases. A reduced expression of MHCI/II-like and T-cell costimulation and signaling activation related transcripts was significantly associated with poor clinical outcome. Moreover, we identified CD70 as a SOX11 direct target gene, whose overexpression was induced in SOX11+ but not SOX11- tumor cells by CD40L in vitro. CD70 was overexpressed in primary SOX11+ MCL and it was associated with an immune unbalance of the tumor microenvironment characterized by increased number of effector Treg cell infiltration, higher proliferation, and aggressive clinical course. CD27 was expressed with moderate to strong intensity in 76% of cases. Overall, our results suggest that SOX11 expression in MCL is associated with an immunosuppressive microenvironment characterized by CD70 overexpression in tumor cells, increased Treg cell infiltration and downmodulation of antigen-processing and -presentation and T-cell activation that could promote MCL progression and represent a potential target for tailored therapies.

scholarly journals Severe CMV infection after chemo-immunotherapy with dose- reduced bendamustine and rituximab in an old mantle cell lymphoma patient

2021 ◽  
Vol 13 (1) ◽  
pp. e2021054
Author(s):  
Gabriele Magliano ◽  
Annarosa Cuccaro ◽  
Francesco D'Alo' ◽  
Elena Maiolo ◽  
Silvia Bellesi ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Male Patient ◽  
Cell Lymphoma ◽  
Lymphoma Patient ◽  
Cmv Infection ◽  
First Line ◽  
Mantle Cell ◽  
Mantle Cell Lymphoma Patient

We discuss the case of a 74-year old male patient with mantle cell lymphoma, who faced severe CMV infection after the fifth cycle of first-line chemo-immunotherapy with a dose-reduced bendamustine and rituximab regimen. 

scholarly journals Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shaojun Zhang ◽  
Vivian Changying Jiang ◽  
Guangchun Han ◽  
Dapeng Hao ◽  
Junwei Lian ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Single Cell ◽  
Communication Networks ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
Survivin Expression ◽  
Therapy Resistance ◽  
Molecular Heterogeneity ◽  
Multiple Cancer ◽  
Mantle Cell

AbstractThe mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Bortezomib Induces an Antioxidant and ER-Stress Response Gene Expression Signature in Mantle Cell Lymphoma: Implications for Response Prediction and Optimized Chemotherapy Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 830-830
Author(s):  
Edgar G. Rizzatti ◽  
Helena Mora-Jensen ◽  
Raymond Lai ◽  
Masanori Daibata ◽  
Therese White ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Er Stress ◽  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Er Stress Response ◽  
Mantle Cell ◽  
Sensitive Group ◽  
Resistant Cells

Abstract Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell lymphoma for which new treatment options are needed. Recent phase II clinical trials reported response to the proteasome inhibitor bortezomib (BZM) in up to 50% of pre-treated patients. Despite the successful use of BZM in the clinic, the precise molecular mechanisms underlying sensitivity or resistance to BZM in MCL remain largely unknown. To address this issue, we used U133A 2.0 microarrays to analyze gene expression in MCL cells from peripheral blood of 5 patients with previously untreated leukemic MCL. Samples were collected immediately before (0h) and at 3, 6, 24, and 72 hours after administration of BZM (1.5 mg/m2). After the blood collection at 72 hours, a second dose of BZM was given, and cells were collected 24 hours later. Two patients had major reductions in peripheral ALC already at 24h from dose 2 and normalized their blood counts by day 21 (sensitive), 1 patient had no change over a full course of 4 injections (resistant), and 2 patients had some decrease in ALC (intermediate). Genes differentially expressed with treatment were ranked according to the degree of correlation with time (Pearson). We used gene set enrichment analysis (GSEA) to detect distinct functional gene expression signatures; the most consistently up-regulated of which was a signature composed by proteasome and chaperone genes. To confirm and expand these findings, we exposed 10 MCL cell lines (7 sensitive, IC50<10nM; 3 resistant IC50>10nM) to 10nM of BZM and analyzed gene expression at 1, 3, 6 and 24 hours. The proteasome signature was again dominant, and the majority of the up-regulated genes in both clinical and cell line samples shared binding motifs for the NRF, MAF, ATF and HSF families of transcription factors (TF). Thus genes up-regulated by BZM in vivo and in cell lines predominantly belonged to a functional response to oxidative and/or endoplasmic reticulum (ER) stress. Under physiologic conditions, this is thought to help restore homeostasis and protect from apoptosis. This response could therefore contribute to drug resistance or be a marker of an overwhelming insult before the cells undergo apoptosis. To address this issue, we investigated differences in response to BZM between sensitive and resistant cell lines. The proteasome signature was more strongly up-regulated in sensitive cells than in resistant cells, and the ER-stress response as measured by genes controlled by the NRF and MAF family of TFs was also more highly expressed in the sensitive group. Consistently, expression of HMOX1, which encodes a key enzyme in the antioxidant response, was increased by 32× at 24h in the sensitive group, but only by 4× in the resistant group; the expression of DDIT3, a transcription factor implicated in a pro-apoptotic response to ER-stress was 5.5-fold up-regulated in the sensitive cells but only 1.4-fold in the resistant cells. We conclude that in sensitive cells BZM induces an overwhelming ER-stress response with high expression of proteasome components and chaperone proteins that could serve as a predictor of response to BZM.

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