CD30

Official Full Name

TNF receptor superfamily member 8

Organism

Homo sapiens

GeneID

943

Background

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB. This receptor is a positive regulator of apoptosis, and also has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Synonyms

CD30; Ki-1; D1S166E;

Protein Sequence

MRVLLAALGLLFLGALRAFPQDRPFEDTCHGNPSHYYDKAVRRCCYRCPMGLFPTQQCPQRPTDCRKQCEPDYYLDEADRCTACVTCSRDDLVEKTPCAWNSSRVCECRPGMFCSTSAVNSCARCFFHSVCPAGMIVKFPGTAQKNTVCEPASPGVSPACASPENCKEPSSGTIPQAKPTPVSPATSSASTMPVRGGTRLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDEAGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARCVPYPICAAETVTKPQDMAEKDTTFEAPPLGTQPDCNPTPENGEAPASTSPTQSLLVDSQASKTLPIPTSAPVALSSTGKPVLDAGPVLFWVILVLVVVVGSSAFLLCHRRACRKRIRQKLHLCYPVQTSQPKLELVDSRPRRSSTQLRSGASVTEPVAEERGLMSQPLMETCHSVGAAYLESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGLAGPAEPELEEELEADHTPHYPEQETEPPLGSCSDVMLSVEEEGKEDPLPTAASGK

Open

Disease

B-cell lymphoma, Diabetes mellitus, Follicular lymphoma, Hodgkin lymphoma, Immune system disease, Immunoproliferative disorder, Leukaemia, Lymphatic vessel/lymph nodes disorder, Lymphoma, Malignant haematopoietic neoplasm, Mature T-cell lymphoma, Multiple myeloma, Mycosis fungoides, Solid tumour/cancer

Approved Drug

1 +

Clinical Trial Drug

21 +

Discontinued Drug

1 +

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Detailed Information

CD30 is a type I transmembrane glycoprotein, characterized by a molecular weight of approximately 120 kDa. Comprising three basic domains—intracellular, transmembrane, and extracellular—it belongs to the TNF receptor superfamily. Essential for ligand binding and receptor oligomerization—a process necessary for later signaling—the extracellular domain consists of repetitive cysteine-rich motifs. The gene shows alternative splicing, producing different isoforms with maybe special regulating purposes. Understanding CD30's biological activity and regulatory roles within the immune system depends on a knowledge of its overall structure and interactions with its ligand, CD30 ligand (CD30L or TNFSF8).

Figure 1 describes how CD30 enhances cell survival through multiple signaling pathways, including the activation of TRAF proteins and the MAPK pathway while highlighting the feedback loop with the JunB transcription factor. Figure 1. CD30 promotes cell survival through diverse signaling pathways. (van der Weyden CA, et al., 2017)

CD30 and Its Role in T Cell Activation

Along with other costimulatory receptors like CD28, CD27, and CD134, T cell activation greatly increases CD30 expression. Usually occurring 4–5 days after T cell receptor (TCR) activation, this upregulation peaks. The expression of CD30 depends on CD28 or IL-4 receptor signaling, therefore highlighting the interdependence of costimulatory systems in T cell activation. Engagement of CD30 improves T cell survival and cytotoxic properties in addition to T cell proliferation. Particularly, CD30 signaling indicates its part in preserving a balance in the immune response by limiting cytotoxic activities.

The regulation of CD30 on T cells has been demonstrated in many studies to modulate peripheral T cell responses, hence regulating their survival and simultaneously down-regulating their cytotoxic capacity. For example, CD30 signaling has been linked to the reduction of effector activities in cytotoxic T lymphocytes (CTLs), therefore implying a mechanism for self-tolerance and avoidance of autoimmune responses. On the other hand, while conflicting findings in various research, CD30 has also been linked with increasing T cell survival during thymic selection processes. The important function of CD30 expression in T cell development and homeostasis is underlined by its interaction with thymocyte selection.

The CD30-CD30L Interaction

Mediating cellular signals influencing lymphocyte behavior depends fundamentally on the interaction between CD30 and its ligand, CD30L. Mostly expressed on activated T cells—especially CD4+ T cells—CD30L helps to provide important signals for B cell development and differentiation. With peak expression levels seen in activated T cells during the first several days after stimulation, CD30L and CD30 have tightly controlled expression dynamics. This temporal control implies a fine-tuning mechanism for immune responses, therefore guaranteeing that CD30 signaling is triggered only in suitable circumstances.

Studies of the CD30-CD30L axis show that stimulation of CD30 may cause downregulation of CD28, a crucial costimulatory receptor needed for T cell activation and proliferation. Such downregulation suggests that T cell responses may be negatively regulated by CD30 signaling, therefore influencing the immunological terrain generally. This phenomenon underlines the complicated interaction of activating and inhibitory signals controlling T cell behavior.

CD30 and Cytotoxicity Regulation

Beyond T cell activation, the consequences of CD30 signaling include the regulation of cytotoxicity in immune cells. Using the YT2C2 natural killer (NK) cell line, CD30 engagement was found to reduce cytotoxic activity against target cells expressing B7 (CD80). Further proving how CD30 may change the interaction between costimulatory signals and cytotoxic responses, the mechanism behind this suppression was connected to a notable downregulation of CD28 expression. Further underscoring its importance in organizing immune cell activities, CD30 stimulation has been linked to alterations in the expression of various surface markers, including CD45 and IL-2 receptor subunits.

Given lymphomas and other cancers, the capacity of CD30 to control cytotoxic activities has significant consequences. Many lymphomas express CD30, so knowledge of its function in these settings might help one to grasp possible treatment approaches aiming at CD30. For example, the presence of CD30 on tumor cells provides a distinct target for monoclonal antibody treatments, which by using the special signaling pathways connected with CD30 may generate strong antitumor responses.

Implications of CD30 in Disease

Not just an activation marker, CD30 has been associated with many pathogenic disorders including anaplastic large-cell lymphoma and peripheral T-cell lymphoma. In oncology, CD30 is a useful biomarker concerning expression patterns and functional consequences. The role of CD30 in regulating T cell responses also extends to autoimmune diseases, where dysregulation of CD30 signaling could contribute to pathological immune responses.

Clinically speaking, CD30 is now a target for therapeutic intervention in lymphoid malignancies. The creation of anti-CD30 monoclonal antibodies offers fresh approaches for treating cancer patients whose tumors exhibit CD30. These treatments highlight the translational importance of CD30 research as they use the processes of immune-mediated cytotoxicity to get therapeutic advantages.

References:

Muta H, Podack ER. CD30: from basic research to cancer therapy. Immunol Res. 2013;57(1-3):151-158.
Herszfeld D, Wolvetang E, Langton-Bunker E, et al. CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotechnol. 2006;24(3):351-357.
van der Weyden CA, Pileri SA, Feldman AL, et al. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. Blood Cancer J. 2017;7(9):e603.

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