Indolent lymphoma: follicular lymphoma and the microenvironment—insights from gene expression profiling

Rimsza, Lisa M.; Jaramillo, Melba C.

doi:10.1182/asheducation-2014.1.163

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…29 In contrary, increased CD8 T cells, but not CD4 T cells, correlate with better clinical outcome in FL, whereas different subpopulations of CD4 T cells restrain or favor B cell growth. 31 Moreover, Vδ1 T cells as a subset of γ/δT cells are also expanded in DLBCL and FL. 27,30 Malignant B cells overexpress inhibitory antigens, including PD-L1, CD200, PVR and CD47 that contribute to the impairment of T cells across B cell malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…In B cell lymphomas, a growing body of evidence indicates that interactions between malignant B cells and immune cells engender an immunosuppressive niche by regulating of immune cell differentiation and recruitment of regulatory T cells (Treg), pDC, suppressive tumor‐associated monocytes/macrophages and myeloid‐derived suppressor cells (MDSC) 6,7,26 . Cytotoxic lymphocytes, including CD8 T cells, γ/δT cells and NK cells play an important role in antilymphoma immunity, especially in diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma (FL) and WM 27‐31 . Recent evidence shows an increase in effector T cell populations, while a decrease in naïve T cells has been detected in a small cohort of patients with WM and IgM MGUS 13 .…”

Section: Discussionmentioning

confidence: 99%

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Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

Cholujová

Beke

Hunter

et al. 2022

Intl Journal of Cancer

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Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

Cholujová

Beke

Hunter

et al. 2022

Intl Journal of Cancer

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“…Clearly, TAMs are biologically linked with FL, presumably providing the proper signals to not only maintain the viability of FL cells but also protect the tumor cells from the active immune system. Based on results of gene expression profiling analysis, investigators found that a defined MP-enriched gene expression pattern was associated with inferior clinical course of FL ( 54 ), indicating that the presence of TAMs in FL patients may predict clinical outcomes. In addition, researchers have used other macrophagic markers identified using immunohistochemistry, such as CD68 and CD163, to predict unfavorable outcomes of FL ( 45 – 47 ).…”

Section: B-cell/mp Interactions In B-cell Lymphomasmentioning

confidence: 99%

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

2018

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Macrophages (MPs) are heterogeneous, multifunctional, myeloid-derived leukocytes that are part of the innate immune system, playing wide-ranging critical roles in basic biological activities, including maintenance of tissue homeostasis involving clearance of microbial pathogens. Tumor-associated MPs (TAMs) are MPs with defined specific M2 phenotypes now known to play central roles in the pathophysiology of a wide spectrum of malignant neoplasms. Also, TAMs are often intrinsic cellular components of the essential tumor microenvironment (TME). In concert with lymphoid-lineage B and T cells at various developmental stages, TAMs can mediate enhanced tumor progression, often leading to poor clinical prognosis, at least partly through secretion of chemokines, cytokines, and various active proteases shown to stimulate tumor growth, angiogenesis, metastasis, and immunosuppression. Researchers recently showed that TAMs express certain key checkpoint-associated proteins [e.g., programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1)] that appear to be involved in T-cell activation and that these proteins are targets of other specific checkpoint-blocking immunotherapies (anti-PD-1/PD-L1) currently part of new therapeutic paradigms for chemotherapy-resistant neoplasms. Although much is known about the wide spectrum and flexibility of MPs under many normal and neoplastic conditions, relatively little is known about the increasingly important interactions between MPs and B-lymphoid cells, particularly in the TME in patients with aggressive B-cell non-Hodgkin lymphoma (NHL-B). Normal and neoplastic lymphoid and myeloid cell/MP lineages appear to share many primitive cellular characteristics as well as transcriptional factor interactions in human and animal ontogenic studies. Such cells are capable of ectopic transcription factor-induced lineage reprogramming or transdifferentiation from early myeloid/monocytic lineages to later induce B-cell lymphomagenesis in experimental in vivo murine systems. Close cellular interactions between endogenous clonal neoplastic B cells and related aberrant myeloid precursor cells/MPs appear to be important interactive components of aggressive NHL-B that we discuss herein in the larger context of the putative role of B-cell/MP cellular lineage interactions involved in NHL-B pathophysiology during ensuing lymphoma development.

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“…17,18 Similar to other B-cell lymphomas, such as follicular lymphoma, the lymph node (LN) microenvironment in CLL is thought to be the predominant site of interaction between the malignant cells and tumor-associated and tumor-specific immune cells. 19 However, data on immune abnormalities in CLL patients are primarily obtained from peripheral blood (PB) studies, and little is known about the composition of nonmalignant lymphocytes in LN tissue or how this relates to PB.…”

Section: Introductionmentioning

confidence: 99%

Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment

et al. 2019

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Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.

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Indolent lymphoma: follicular lymphoma and the microenvironment—insights from gene expression profiling

Cited by 10 publications

References 40 publications

Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia

The Role of Macrophage/B-Cell Interactions in the Pathophysiology of B-Cell Lymphomas

Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment

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