The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

Zhou, Xiaolan; Mulazzani, Matthias; Mücke-Heim, Iven-Alex von; Langer, Sigrid; Zhang, Wenlong; Ishikawa-Ankerhold, Hellen; Dreyling, Martin; Straube, Andreas; Baumgarten, Louisa von

doi:10.3389/fonc.2020.00682

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…The in vivo -formation of brain metastasis was assessed in the cranial window model using two-photon laser scanning-microscopy. In contrast to conventional histological methods, this technique allows for repetitive analysis of tumor cells and TAM/M at single cell resolution [ 41 , 42 ]. Thus, we were able to reliably visualize brain metastasis growth.…”

Section: Discussionmentioning

confidence: 99%

In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer

et al. 2021

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Brain metastases frequently occur in lung cancer and dramatically limit prognosis of affected patients. The influence of tumor-associated macrophages and microglia (TAM/M) and their receptor CX3CR1 on different steps of brain metastasis formation from lung cancer is poorly characterized. We established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intravital 2-photon laser scanning microscopy. This allowed in vivo tracking of fluorescence-expressing tumor cells and TAM/M on a single-cell level over weeks. Intracarotid injection of red tdTomato-fluorescent Lewis lung carcinoma cell was performed in transgenic mice either proficient or deficient for CX3CR1. After intracarotid cell injection, intravascular tumor cells extravasated into the brain parenchyma and formed micro- and mature macrometastases. We observed potential phagocytosis of extravasated tumor cells by TAM/M. However, during later steps of metastasis formation, these anti-tumor effects diminished and were paralleled by TAM/M accumulation and activation. Although CX3CR1 deficiency resulted in a lower number of extravasated tumor cells, progression of these extravasated cells into micro metastases was more efficient. Overall, this resulted in a comparable number of mature macrometastases in CX3CR1-deficient and -proficient mice. Our findings indicate that unspecific inhibition of CX3CR1 might not be a suitable therapeutic option to prevent dissemination of lung cancer cells to the brain. Given the close interaction between TAM/M and tumor cells during metastasis formation, other therapeutic approaches targeting TAM/M function may warrant further evaluation. The herein established orthotopic mouse model may be a useful tool to evaluate such concepts in vivo .

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Section: Discussionmentioning

confidence: 99%

In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer

et al. 2021

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“…For indirect immunofluorescence staining, the following primary and secondary antibodies were used: Human CD20 (1:200, Abcam, Cambridge, UK, ab194970) [ 61 ], human/mouse CD44 (1:400, Thermo Fisher Scientific, Waltham, Massachusetts, USA, 14-0441-82) [ 62 ], mouse CXCR4 (1:25, Bio-Techne, Minneapolis, Minnesota, USA, MAB21651) [ 63 ], mouse/human CXCR5 (1:100, Abcam, ab133706) [ 64 , 65 , 66 , 67 ], mouse/human CXCR7 (1:200, Abcam, ab72100) [ 63 ], Donkey Anti-goat DyLight550 (1:200, Thermo Fisher Scientific, SA5-10087), Donkey anti-rat AlexaFluor 488 (1:200, Thermo Fisher Scientific, A21208) and Donkey anti-rabbit DyLight488 (1:200, Thermo Fisher Scientific, SA5-10038).…”

Section: Methodsmentioning

confidence: 99%

CXCR4, CXCR5 and CD44 May Be Involved in Homing of Lymphoma Cells into the Eye in a Patient Derived Xenograft Homing Mouse Model for Primary Vitreoretinal Lymphoma

Babst

Isbell

Rommel

et al. 2022

IJMS

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Background: Primary vitreoretinal lymphoma (PVRL), a rare malignancy of the eye, is strongly related to primary central nervous system lymphoma (PCNSL). We hypothesized that lymphoma cells disseminate to the CNS and eye tissue via distinct homing receptors. The objective of this study was to test expression of CXCR4, CXCR5, CXCR7 and CD44 homing receptors on CD20 positive B-lymphoma cells on enucleated eyes using a PCNSL xenograft mouse model. Methods: We used indirect immunofluorescence double staining for CD20/CXCR4, CD20/CXCR5, CD20/CXCR7 and CD20/CD44 on enucleated eyes of a PCNSL xenograft mouse model with PVRL phenotype (PCNSL group) in comparison to a secondary CNS lymphoma xenograft mouse model (SCNSL group). Lymphoma infiltration was evaluated with an immunoreactive score (IRS). Results: 11/13 paired eyes of the PCNSL but none of the SCNSL group were infiltrated by CD20-positive cells. Particularly the choroid and to a lesser extent the retina of the PCNSL group were infiltrated by CD20+/CXCR4+, CD20+/CXCR5+, few CD20+/CD44+ but no CD20+/CXCR7+ cells. Expression of CXCR4 (p = 0.0205), CXCR5 (p = 0.0004) and CD44 (p < 0.0001) was significantly increased in the PCNSL compared to the SCNSL group. Conclusions: CD20+ PCNSL lymphoma cells infiltrating the eye co-express distinct homing receptors such as CXCR4 and CXCR5 in a PVRL homing mouse model. These receptors may be involved in PVRL homing into the eye.

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“…BCMA (also known as tumor necrosis factor receptor superfamily member 17/TNFRS17) is a transmembrane protein that contains cysteine-rich extracellular domains and lacks a signal peptide [ 267 ]. Along with the related TNFR superfamily member BAFF-R, BCMA critically regulates B cell proliferation, survival and differentiation into plasma cells [ 102 , 267 , 268 ]. BCMA is expressed at significantly higher levels by MM cells ( Table 1 ) than by normal tissues (except for normal plasma cells) [ 269 ].…”

Section: Clinical Trials Of Novel Anti-taa Inhibitors In the Treatmen...mentioning

confidence: 99%

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Tannoury

Garnier

Susin

et al. 2022

Cancers

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Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders.

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The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

Cited by 11 publications

References 48 publications

In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer

In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer

CXCR4, CXCR5 and CD44 May Be Involved in Homing of Lymphoma Cells into the Eye in a Patient Derived Xenograft Homing Mouse Model for Primary Vitreoretinal Lymphoma

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

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