CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

Bobrowicz, Małgorzata; Kubacz, Matylda; Ślusarczyk, Aleksander; Winiarska, Magdalena

doi:10.3390/ijms21249531

Cited by 21 publications

(18 citation statements)

References 89 publications

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“…Similar to the malignant T-cell clone (T-4), the B-1 population was characterized by a decrease in CXCR4 and CD69 tissue-homing markers when compared with benign B cells from cluster B-2, but also showed upregulation of genes involved in cell motility (ACTB, ACTG1, MYL6, ACTG2) and glucose metabolism (PGAM1, TPI1, GAPDH, MDH1, PKM) (Figure 5a and Table S8; see Supporting Information), which might indicate increased metabolic activity. 25 We also found decreases in the tetraspanin family member CD37, a negative regulator of B-cell lymphomagenesis, 26 and of the alemtuzumab target CD52 (Figure 5a). In line with the indolent nature of PCFCL, we observed downregulation of markers previously associated with a more aggressive lymphoma phenotype, including the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) gene, known to promote tumorigenesis and immune escape of diffuse large B-cell lymphoma (DLBCL), 27 or T-cell leukaemia/lymphoma protein 1A (TCL1A), associated with worse prognosis in DLBCL.…”

Section: B-cell Lymphoma Clone Characteristicsmentioning

confidence: 80%

Single‐cell RNA sequencing profiling in a patient with discordant primary cutaneous B‐cell and T‐cell lymphoma reveals micromilieu‐driven immune skewing

et al. 2021

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Summary Background Primary cutaneous lymphomas comprise a heterogeneous group of B‐cell and T‐cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood. Objectives To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. Methods Single‐cell RNA sequencing (scRNA‐seq) was performed and combined with T‐cell and B‐cell receptor sequencing. Results We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type‐2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro‐oncogenic genes. By contrast, PCFCL lesions exhibited a more type‐1 immune phenotype, consistent with its indolent behaviour. Conclusions These data not only illustrate the diagnostic potential of scRNA‐seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

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Section: B-cell Lymphoma Clone Characteristicsmentioning

confidence: 80%

Single‐cell RNA sequencing profiling in a patient with discordant primary cutaneous B‐cell and T‐cell lymphoma reveals micromilieu‐driven immune skewing

et al. 2021

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“…CD37 is expressed almost exclusively on hematopoietic cells with high expression on mature B-cells, including their malignant counterparts [ 331 ]. A large number of CD37 targeting agents have been developed including mAbs, ARCs, ADCs, and CAR-T cells [ 332 , 333 , 334 , 335 ]. Among them, the anti-CD37 BI856826, initially reported as a valid therapeutic target in B-NHL (NCT01403948) [ 336 ] and CLL (NCT02759016) [ 334 ], did not undergo further clinical development upon the decision of sponsors to discontinue the trials.…”

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 approval of polatuzumab vedotin in combination with bendamustine and rituximab in r/r DLBCL was preceded by a clinical trial that for the first time after several years demonstrated the benefit in OS to an experimental arm of the study [154]. Besides the above-mentioned targets, an attractive alternative is the use of CD37-directed mAbs, which are currently in clinical trials and we have recently reviewed them in [157].…”

Section: Other Treatment Modalities As Possible Solutions For Relapse...mentioning

confidence: 99%

Molecular Aspects of Resistance to Immunotherapies—Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma

Kusowska

Kubacz

Krawczyk

et al. 2022

IJMS

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Despite the unquestionable success achieved by rituximab-based regimens in the management of diffuse large B-cell lymphoma (DLBCL), the high incidence of relapsed/refractory disease still remains a challenge. The widespread clinical use of chemo-immunotherapy demonstrated that it invariably leads to the induction of resistance; however, the molecular mechanisms underlying this phenomenon remain unclear. Rituximab-mediated therapeutic effect primarily relies on complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, and their outcome is often compromised following the development of resistance. Factors involved include inherent genetic characteristics and rituximab-induced changes in effectors cells, the role of ligand/receptor interactions between target and effector cells, and the tumor microenvironment. This review focuses on summarizing the emerging advances in the understanding of the molecular basis responsible for the resistance induced by various forms of immunotherapy used in DLBCL. We outline available models of resistance and delineate solutions that may improve the efficacy of standard therapeutic protocols, which might be essential for the rational design of novel therapeutic regimens.

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CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

Cited by 21 publications

References 89 publications

Single‐cell RNA sequencing profiling in a patient with discordant primary cutaneous B‐cell and T‐cell lymphoma reveals micromilieu‐driven immune skewing

Single‐cell RNA sequencing profiling in a patient with discordant primary cutaneous B‐cell and T‐cell lymphoma reveals micromilieu‐driven immune skewing

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

Molecular Aspects of Resistance to Immunotherapies—Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma

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