CD37

Official Full Name

CD37 molecule

Organism

Homo sapiens

GeneID

951

Background

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It may play a role in T-cell-B-cell interactions. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Synonyms

GP52-40; TSPAN26;

Bio Chemical Class

Tetraspanin

Protein Sequence

MSAQESCLSLIKYFLFVFNLFFFVLGSLIFCFGIWILIDKTSFVSFVGLAFVPLQIWSKVLAISGIFTMGIALLGCVGALKELRCLLGLYFGMLLLLFATQITLGILISTQRAQLERSLRDVVEKTIQKYGTNPEETAAEESWDYVQFQLRCCGWHYPQDWFQVLILRGNGSEAHRVPCSCYNLSATNDSTILDKVILPQLSRLGHLARSRHSADICAVPAESHIYREGCAQGLQKWLHNNLISIVGICLGVGLLELGFMTLSIFLCRNLDHVYNRLARYR

Open

Disease

Diffuse large B-cell lymphoma, Leukaemia, Malignant haematopoietic neoplasm, Mature B-cell leukaemia, Mature T-cell lymphoma, Solid tumour/cancer

Approved Drug

Clinical Trial Drug

7 +

Discontinued Drug

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Detailed Information

CD37 is a gene that encodes a protein belonging to the tetraspanin family, a large family of membrane proteins. These proteins are typically characterized by four hydrophobic domains and are located on the cell membrane, where they play critical roles in regulating various cellular functions, including signal transduction, cell development, activation, motility, and adhesion. Mostly expressed in B cells, the CD37 protein is found most especially on the surface of both normal and malignant B cells. Although CD37 is less often expressed on other hematopoietic cells such as T cells, NK cells, and dendritic cells, its interaction with many biological processes makes it nevertheless a key immune regulator.

Structural Features and Function of CD37

Considered a tetraspanin, CD37 crosses the cell membrane four times. Three transmembrane areas plus tiny intracellular and extracellular loops characterize the structure of tetraspans. One characteristic of tetraspanins is a conserved CCG motif on the big extracellular loop. Interacting with other surface proteins, cytoskeletal components, and receptors, these proteins help to arrange membrane domains and enable signal transmission.

Acting as a structural component of tetraspanin-enriched microdomains (TEMs), CD37 mostly serves Receptor clustering and signaling to find a stage in these microdomains, therefore controlling a range of biological processes including cell adhesion, migration, protein trafficking, and immune cell activation. Employing these mechanisms, CD37 helps to control the immune system, survive, and cause the death of B cells.

Role in Immune Function

Particularly in the survival and activation of B cells, CD37 is essential for immune cell activity. It helps B cells migrate and adhere to other cells, therefore altering their sensitivity to environmental stimuli. Moreover, integrin clustering on B cell membranes is under impact by CD37, which is essential for immune systems. It may also trigger death via interactions with other signaling molecules like LYN, SHP1, and SYK, and survival pathways through the PI3K/AKT signaling cascade are promoted. Additionally interacting with SOCS3, CD37 controls the IL-6 signaling pathway, therefore limiting too strong inflammatory reactions.

Apart from its function in B cells, CD37 is also engaged in the immunological response of dendritic cells and neutrophils, therefore enabling their migration to lymph nodes and supporting their adherence. Key in both innate and adaptive immune responses, its capacity to bind with integrins and alter immune signaling pathways drives this action.

Figure 1 describes the involvement of CD37 in B cells in both activatory and inhibitory signaling pathways. Figure 1. CD37 in B cells regulates both activatory (PI3Kδ/p-Akt/p-GSK3/β-catenin) and inhibitory (SHP1/p-Akt/Foxo3; SOCS3/Jak) signaling pathways. (Bobrowicz M, et al., 2020)

CD37 in Disease and Cancer

Among numerous hematological cancers, CD37 has been linked to T cell lymphoma and B cell non-Hodgkin lymphoma (B-NHL). Still, CD37 expression in cancer is not consistent. Only around 60% of follicular lymphoma (FL) and 40% of diffuse large B cell lymphoma (DLBCL) tumors express CD37, suggesting that it is not a universal marker for all B cell malignancies according to studies.

Rare T cell malignancies, including T cell lymphoma, as well as in rare cases acute myeloid leukemia (AML), also show CD37 expression. This fluctuation in expression implies that CD37 could be more important as a therapeutic target in certain subtypes of cancer, especially those including B cell malignancies. With various monoclonal antibodies and antibody-based treatments in development to target CD37 on tumor cells, CD37's significance in B cell malignancies makes it a desirable target for immunotherapy.

Targeting CD37 using chimeric antigen receptor T cell (CAR-T) treatment has been proven recently to improve anti-tumor immunity. Scarfò et al. for instance showed that, without generating any bystander damage, CD37-targeted CAR-T cells could drive antigen-dependent activation, cytokine production, and tumor cell death in vitro. Still, not all PTCL (peripheral T-cell lymphoma) cell lines or patient samples express CD37, so further study is required to pinpoint patients most likely to benefit from such treatments.

CD37 and Immunotherapy

CD37 is a promising target for therapeutic approaches as it is expressed on both benign and malignant B cells. Among the most important uses of CD37 targeting is immunotherapy, especially for monoclonal antibody usage. These antibodies designate tumor cells for immune system destruction by binding especially to CD37. Preclinical models and clinical studies of recent developments in CAR-T cell therapy—which entails designing T cells to target CD37—have also shown encouraging outcomes.

Treatment of refractory individuals with B-cell malignancies benefits especially from CD37 targeting in immunotherapy. Blocking CD37's interaction with other signaling molecules might assist in stopping immune evasion strategies used by cancer cells. Still, there are difficulties as CD37 expresses itself differently in many kinds of lymphoma and leukemia. Future studies should therefore concentrate on the identification of biomarkers able to forecast CD37 expression in tumor cells and direct patient choice for CD37-targeted treatments.

References:

Caulier B, Joaquina S, Gelebart P, et al. CD37 is a safe chimeric antigen receptor target to treat acute myeloid leukemia. Cell Rep Med. 2024;5(6):101572.
Bobrowicz M, Kubacz M, Slusarczyk A, et al. CD37 in B Cell Derived Tumors-More than Just a Docking Point for Monoclonal Antibodies. Int J Mol Sci. 2020;21(24):9531.
Payandeh Z, Noori E, Khalesi B, et al. Anti-CD37 targeted immunotherapy of B-Cell malignancies. Biotechnol Lett. 2018;40(11-12):1459-1466.

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