Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL)

Farinha, Pedro; Masoudi, Hamid; Skinnider, Brian; Shumansky, Karey; Spinelli, John J.; Gill, Karamjit; Klasa, Richard; Voss, Nicholas; Connors, Joseph M.; Gascoyne, Randy D.

doi:10.1182/blood-2005-04-1565

Cited by 419 publications

(353 citation statements)

References 40 publications

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“…21 Farinha et al 22 suggested that a high number of tumor-associated macrophages (Z15 CD68 þ macrophages/HPF) were correlated with a poor prognosis (5.0 years) in 12 of the 99 follicular lymphoma cases as opposed to 87 cases with o15 CD68 þ macrophages/HPF (16.3 years). In this respect, we found more than five macrophages/ HPF in 5% of our cases and this was also correlated with poorer overall survival compared with the group with r5 macrophages/HPF (7.6 vs 14 years, respectively).…”

Section: Discussionmentioning

confidence: 99%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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“…29,30 Finally, a high number of CD68 pos TAM predicts an unfavorable outcome in FL patients. 7,30 These observations raise the hypothesis that monocyte-derived IL-15 and T-cell-derived CD40L could cooperate to promote malignant B-cell growth in FL.…”

Section: Il-15 Stimulates Primary Fl B-cell Growth In the Presence Ofmentioning

confidence: 85%

“…6 Finally, microarray gene expression studies, quantitative-PCR analyses and immunohistochemical experiments suggest that a high numbers of CD68 pos or CD163 pos tumor-associated macrophages (TAM) is of bad prognosis in FL patients treated with chemotherapy not associated with antibody-based immunotherapy. [7][8][9][10][11] Moreover, in diffuse large B-cell lymphomas, the most frequent aggressive GC-derived lymphoma, monocytes deliver survival signals to malignant B cells at least in part through the production of B-cell activating factor (BAFF). 12 Nevertheless, how TAM favor FL B-cell growth in situ and what could be the cooperative role of neighboring T cells in this context have not been considered.…”

Section: Introductionmentioning

confidence: 99%

Monocytes and T cells cooperate to favor normal and follicular lymphoma B-cell growth: role of IL-15 and CD40L signaling

et al. 2011

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Interleukin-15 (IL-15) has been extensively studied for its role in the survival and proliferation of NK and T cells through a unique mechanism of trans-presentation by producer cells. Conversely, whereas activated B cells have been described as IL-15-responding cells, the cellular and molecular context sustaining this effect remains unexplored. In this study, we found that, whereas human B cells could not respond to soluble IL-15, monocytes and lymphoid tissue-derived macrophages but not stromal cells efficiently trans-present IL-15 to normal B cells and cooperate with T-cell-derived CD40L to promote IL-15-dependent B-cell proliferation. Furthermore, CD40L signaling triggers a Src-independent upregulation of STAT5 expression and favors a Src-dependent phosphorylation of STAT5 in response to IL-15. In follicular lymphoma (FL), immunohistochemical studies reported a strong relationship between malignant B cells, infiltrating macrophages and T cells. We show here an overexpression of IL-15 in purified tumor-associated macrophages, and STAT5A in purified tumor B cells. Moreover, FL B cells respond to IL-15 trans-presented by monocytes/macrophages, in particular, in the presence of CD40L-mediated signaling. This cooperation between IL-15 and CD40L reinforces the importance of tumor microenvironment and unravels a mechanism of FL growth that should be considered if using IL-15 as a drug in this disease.

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“…Although the cell lineage markers employed in this study do not permit further delineation of the identity of the non-B/non-T cell population, it is likely that these cells encompass, at least in part, monocyte/macrophage lineage cells. The frequency of CD68þ macrophages in follicular lymphoma has been previously correlated with poorer overall survival (19). In that study, 12 of 99 cases demonstrated more than 15 CD68þ macrophages per high power field.…”

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confidence: 79%

CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma

Dakappagari

Gascoyne

et al. 2011

Cytometry Part B Clinical

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Background: CD80 is a member of the B7 family of immune coregulatory proteins that mediate both immune activation and suppression. CD80 in particular has recently been shown to play an important role in supporting immune suppression through interactions with B7-H1. CD80 has been identified as a therapeutic target in non-Hodgkin lymphoma (NHL) based on limited immunohistochemical studies of CD80 expression. Clinical studies have shown that the anti-CD80 antibody galiximab is safe and clinically efficacious in follicular NHL. However, the mechanisms through which targeting CD80 inhibits tumor progression remain poorly understood.Methods: To further define the potential of CD80 as a therapeutic target in NHL, CD80 expression was evaluated by multicolor flow cytometric analysis of primary lymphoma cell suspensions generated from 241 diagnostic biopsies of patients with NHL.Results: CD80 was expressed on malignant B cells in essentially all cases of follicular lymphoma (97%; n 5 115), the majority of cases of diffuse large B-cell lymphoma (90%; n 5 69), marginal zone lymphoma (91%; n 5 22), mantle cell lymphoma (75%; n 5 12), and in about half of small lymphocytic lymphoma cases (43%; n 5 23). CD80 was also present on tumor-infiltrating T lymphocytes in nearly all cases. Additionally, CD80 was expressed by non-B, non-T cells in 68 and 44% of cases of follicular and diffuse large B-cell NHL, respectively.Conclusions: CD80 is expressed on both malignant cells and the nonmalignant cells in NHL. Therapeutic targeting of CD80 will therefore modulate the complex intercellular interactions that define the tumor microenvironment in NHL. V C 2011 International Clinical Cytometry Society

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Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL)

Cited by 419 publications

References 40 publications

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Monocytes and T cells cooperate to favor normal and follicular lymphoma B-cell growth: role of IL-15 and CD40L signaling

CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma

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