CD30 explained

CD30, also known as TNFRSF8 (TNF receptor superfamily member 8),^[1] is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker.

Function

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.^[2] It is a positive regulator of apoptosis,^[3] 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.^[1]

Clinical significance

CD30 is associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma but not in seminoma and is thus a useful marker in distinguishing between these germ cell tumors.^[4] CD30 and CD15 are also expressed on Reed-Sternberg cells typical for Hodgkin's lymphoma.^[5]

Cancer treatment

CD30 is the target of the FDA approved therapeutic brentuximab vedotin (Adcetris). It is approved for use in:

1. Hodgkin lymphoma (HL) (brentuximab vedotin) after failure of autologous stem cell transplant (ASCT)
2. HL in patients who are not ASCT candidates after failure of at least 2 multiagent chemotherapy regimens
3. Systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 multiagent chemotherapy regimen^[6]
4. Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy^[7]
5. Various types of CD30-positive T cell lymphomas^[8]

Brentuximab vedotin is also currently being studied in and recommended for treating:

1. Various types of CD30-positive B cell lymphomas^[9]
2. CD30-positive cases of the NK cell lymphoma, extranodal NK/T-cell lymphoma, nasal type^[10]

Interactions

CD30 has been shown to interact with TRAF5,^[2] and TRAF2.^{[2] [3]}

Further reading

• Schneider C, Hübinger G . Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family . Leukemia & Lymphoma . 43 . 7 . 1355–66 . Jul 2002 . 12389614 . 10.1080/10428190290033288 . 12699308 .
• Horie R, Higashihara M, Watanabe T . Hodgkin's lymphoma and CD30 signal transduction . International Journal of Hematology . 77 . 1 . 37–47 . Jan 2003 . 12568298 . 10.1007/BF02982601 . 24727080 .
• Tarkowski M . Expression and a role of CD30 in regulation of T-cell activity . Current Opinion in Hematology . 10 . 4 . 267–71 . Jul 2003 . 12799531 . 10.1097/00062752-200307000-00003 . 37330851 .
• Granados S, Hwang ST . Roles for CD30 in the biology and treatment of CD30 lymphoproliferative diseases . The Journal of Investigative Dermatology . 122 . 6 . 1345–7 . Jun 2004 . 15175022 . 10.1111/j.0022-202X.2004.22616.x . free .
• Dürkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H . Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease . Cell . 68 . 3 . 421–7 . Feb 1992 . 1310894 . 10.1016/0092-8674(92)90180-K . 7999537 .
• Fonatsch C, Latza U, Dürkop H, Rieder H, Stein H . Assignment of the human CD30 (Ki-1) gene to 1p36 . Genomics . 14 . 3 . 825–6 . Nov 1992 . 1330892 . 10.1016/S0888-7543(05)80203-4 .
• Josimovic-Alasevic O, Dürkop H, Schwarting R, Backé E, Stein H, Diamantstein T . Ki-1 (CD30) antigen is released by Ki-1-positive tumor cells in vitro and in vivo. I. Partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture supernatants and in serum by an enzyme-linked immunosorbent assay . European Journal of Immunology . 19 . 1 . 157–62 . Jan 1989 . 2537734 . 10.1002/eji.1830190125 . 29049745 .
• Stein H, Gerdes J, Schwab U, Lemke H, Mason DY, Ziegler A, Schienle W, Diehl V . Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population . International Journal of Cancer . 30 . 4 . 445–59 . Oct 1982 . 6754630 . 10.1002/ijc.2910300411 . 24167082 .
• Jung W, Krueger S, Renner C, Gause A, Sahin U, Trümper L, Pfreundschuh M . Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources . Molecular Immunology . 31 . 17 . 1329–34 . Dec 1994 . 7527901 . 10.1016/0161-5890(94)90051-5 .
• Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S . Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3 . Oncogene . 9 . 6 . 1567–74 . Jun 1994 . 8183550 .
• Lee SY, Park CG, Choi Y . T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors . The Journal of Experimental Medicine . 183 . 2 . 669–74 . Feb 1996 . 8627180 . 2192463 . 10.1084/jem.183.2.669 .
• Gedrich RW, Gilfillan MC, Duckett CS, Van Dongen JL, Thompson CB . CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins . The Journal of Biological Chemistry . 271 . 22 . 12852–8 . May 1996 . 8662842 . 10.1074/jbc.271.22.12852 . free .
• Horie R, Ito K, Tatewaki M, Nagai M, Aizawa S, Higashihara M, Ishida T, Inoue J, Takizawa H, Watanabe T . A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages . Blood . 88 . 7 . 2422–32 . Oct 1996 . 10.1182/blood.V88.7.2422.bloodjournal8872422 . 8839832 . free .
• Aizawa S, Nakano H, Ishida T, Horie R, Nagai M, Ito K, Yagita H, Okumura K, Inoue J, Watanabe T . Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation . The Journal of Biological Chemistry . 272 . 4 . 2042–5 . Jan 1997 . 8999898 . 10.1074/jbc.272.4.2042 . free .
• Lee SY, Lee SY, Choi Y . TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation . The Journal of Experimental Medicine . 185 . 7 . 1275–85 . Apr 1997 . 9104814 . 2196258 . 10.1084/jem.185.7.1275 .
• Boucher LM, Marengère LE, Lu Y, Thukral S, Mak TW . Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily . Biochemical and Biophysical Research Communications . 233 . 3 . 592–600 . Apr 1997 . 9168896 . 10.1006/bbrc.1997.6509 .
• Duckett CS, Thompson CB . CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival . Genes & Development . 11 . 21 . 2810–21 . Nov 1997 . 9353251 . 316646 . 10.1101/gad.11.21.2810 .
• Mizushima S, Fujita M, Ishida T, Azuma S, Kato K, Hirai M, Otsuka M, Yamamoto T, Inoue J . Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5) . Gene . 207 . 2 . 135–40 . Jan 1998 . 9511754 . 10.1016/S0378-1119(97)00616-1 .
• Kurts C, Carbone FR, Krummel MF, Koch KM, Miller JF, Heath WR . Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells . Nature . 398 . 6725 . 341–4 . Mar 1999 . 10192335 . 10.1038/18692 . 1999Natur.398..341K . 19212457 .

Notes and References

1. Web site: Entrez Gene: TNFRSF8 tumor necrosis factor receptor superfamily member 8. National Library of Medicine, National Center for Biotechnology Information. 22 September 2022. 6 November 2022.
2. Aizawa S, Nakano H, Ishida T, Horie R, Nagai M, Ito K, Yagita H, Okumura K, Inoue J, Watanabe T . 6 . Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation . The Journal of Biological Chemistry . 272 . 4 . 2042–2045 . January 1997 . 8999898 . 10.1074/jbc.272.4.2042 . free .
3. Duckett CS, Thompson CB . CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival . Genes & Development . 11 . 21 . 2810–2821 . November 1997 . 9353251 . 316646 . 10.1101/gad.11.21.2810 . free .
4. Teng LH, Lu DH, Xu QZ, Fu YJ, Yang H, He ZL . [Expression and diagnostic significance of OCT4, CD117 and CD30 in germ cell tumors] . zh . Zhonghua Bing Li Xue Za Zhi Chinese Journal of Pathology . 34 . 11 . 711–5 . Nov 2005 . 16536313 .
5. Gorczyca W, Tsang P, Liu Z, Wu CD, Dong HY, Goldstein M, Cohen P, Gangi M, Weisberger J . CD30-positive T-cell lymphomas co-expressing CD15: an immunohistochemical analysis . International Journal of Oncology . 22 . 2 . 319–24 . Feb 2003 . 12527929 . 10.3892/ijo.22.2.319 .
6. Deng C, Pan B, O'Connor OA . Brentuximab vedotin . Clinical Cancer Research . 19 . 1 . 22–7 . Jan 2013 . 23155186 . 10.1158/1078-0432.CCR-12-0290 . free .
7. Web site: FDA approves Brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma . FDA.gov . March 2, 2018.
8. Web site: FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot . FDA.gov . 24 March 2020 . December 13, 2023.
9. Berger GK, McBride A, Lawson S, Royball K, Yun S, Gee K, Bin Riaz I, Saleh AA, Puvvada S, Anwer F . Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review . Critical Reviews in Oncology/Hematology . 109 . 42–50 . January 2017 . 28010897 . 5218629 . 10.1016/j.critrevonc.2016.11.009 .
10. Hu B, Oki Y . Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma . Frontiers in Oncology . 8 . 139 . 2018 . 29761078 . 5937056 . 10.3389/fonc.2018.00139 . free .