Differentiation of Malignant B-Lymphoma Cells from Normal and Activated T-Cell Populations by Their Intrinsic Autofluorescence

Pantanelli, Seth; Li, Zhuqing; Fariss, Robert N.; Mahesh, Sankaranarayana P.; Liu, Baoying; Nussenblatt, Robert B.

doi:10.1158/0008-5472.can-08-2761

Cited by 17 publications

(21 citation statements)

References 27 publications

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“…20 Each cell population was effectively isolated based on their emissions when excited with different wavelengths. The intensity differences that allowed cell type differentiation were believed to be the result of the relative increase in aerobic energy metabolism of the B cell.…”

Section: Discussionmentioning

confidence: 99%

Fundus Autofluorescence Patterns in Primary Intraocular Lymphoma

Casady

Faia

Nazemzadeh

et al. 2014

Retina

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Section: Discussionmentioning

confidence: 99%

Fundus Autofluorescence Patterns in Primary Intraocular Lymphoma

Casady

Faia

Nazemzadeh

et al. 2014

Retina

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“…Autofluorescence of B-cell lymphoma compared to normal T-cells has been demonstrated when the cells were excited by 488 nm light (Pantanelli et al, 2009), and emitted light at 530–540 nm. Alexa-488 was used to evaluate LLP2A, and emits light from 400 to 650 nm, detected through the 542–585 filter, which was in a similar range.…”

Section: Discussionmentioning

confidence: 99%

Affinity of the alpha4–beta1 integrin-targeting peptide LLP2A to canine lymphoma

Zwingenberger

Kent

Shi

et al. 2012

Veterinary Immunology and Immunopathology

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Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4–beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4–beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.

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“…Data concerning the immune microenvironment of PIOL are scarce due to the location of the tumor in the eye. Only few cytopathological studies report the presence of T cell infiltration in patients with intraocular B cell lymphoma [87], but our immunocompetent PIOL mouse model confirmed the concomitant infiltration of immune cells (e.g., CD4 + and CD8 + T cells, monocytes/macrophages, polymorphonuclear neutrophils) during tumor growth [88]. Similarly, a T cell infiltration of the brain with CD4+ and CD8+ T cells during growth of the murine A.20IIA lymphomatous B cell line was observed in BALB/c mice (Fisson et al, under preparation).…”

Section: The Influence Of the Tumor Microenvironment In Cns Lymphomamentioning

confidence: 99%

Tumor microenvironment is multifaceted

Sautès-Fridman

Cherfils‐Vicini

Damotte

et al. 2011

Cancer Metastasis Rev

103

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Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the hosts and sites where tumors develop. Tumors arising in mucosal tissues may progress in an inflammatory context linked to local viral and/or bacterial infections. At the opposite, tumors developing in immunoprivileged sites are protected from microorganisms and grow in an immunosuppressive environment. In the present review, we summarize and present our recent data on the influence of infectious context and immune cell infiltration organization in human Non-Small Cell Lung Cancers (NSCLC) progression. We show that stimulation of tumor cells by TLR for viral ssRNA, such as TLR7/8, or bacteria, such as TLR4, promotes cell survival and induces chemoresistance. On the opposite, stimulation by TLR3, receptor for double-stranded viral RNA, decreases tumor cell viability and induces chemosensitivity in some lung tumor cell lines. Since fresh lung tumor cells exhibit a gene expression profile characteristic of TLR-stimulated lung tumor cell lines, we suspect that viral and bacterial influence may not only act on the host immune system but also directly on tumor growth and sensitivity to chemotherapy. The stroma of NSCLC contains tertiary lymphoid structures (or Tumor-induced Bronchus-Associated Lymphoid Tissues (Ti-BALT)) with mature DC, follicular DC, and T and B cells. Two subsets of immature DC, Langerhans cells (LC) and interstitial DC (intDC), were detected in the tumor nests and the stroma, respectively. Here, we show that the densities of the three DC subsets, mature DC, LC, and intDC, are highly predictive of disease-specific survival in a series of 74 early-stage NSCLC patients. We hypothesize that the mature DC may derive from local activation and migration of the immature DC--and especially LC which contact the tumor cells--to the tertiary lymphoid structures, after sampling and processing of the tumor antigens. In view of the prominent role of DC in the immune response, we suggest that the microenvironment of early-stage NSCLC may allow the in situ activation of the adaptive response. Finally, we find that the eyes or brain of mice with growing B cell lymphoma are infiltrated with T cells and that the cytokines produced ex vivo by the tumoral tissues have an impaired Th1 cytokine profile. Our work illustrates that the host and external tumor microenvironments are multifaceted and strongly influence tumor progression and anti-tumor immune responses.

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Differentiation of Malignant B-Lymphoma Cells from Normal and Activated T-Cell Populations by Their Intrinsic Autofluorescence

Abstract: Patients with active posterior and intermediate uveitis have inflammatory cells in their vitreous; those with primary intraocular lymphoma have malignant B-lymphoma cells concomitantly. These cell types cannot be distinguished clinically.

Cited by 17 publications

References 27 publications

Fundus Autofluorescence Patterns in Primary Intraocular Lymphoma

Fundus Autofluorescence Patterns in Primary Intraocular Lymphoma

Affinity of the alpha4–beta1 integrin-targeting peptide LLP2A to canine lymphoma

Tumor microenvironment is multifaceted

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