CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily that is expressed on activated lymphocytes, as well as on neoplastic cells of Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL).
Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas that are characterized by CD30 expression.
Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma.
In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody.
Patients respond well to chemotherapy with cure rates of 80-90% and the recent finding of PD-L1 expression, an immune checkpoint, warrants the use of immunotherapy for some patients with recurrent and/or refractory HL.
In 2011, the ADC brentuximab-vedotin, consisting of the CD30-specific chimeric mAb cAC10 and the potent tubulin toxin monomethyl auristatin E, gained regulatory approval as a well tolerated and highly active drug in patients with refractory and relapsed HL and ALCL.
CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas.
Reporter gene assays revealed that the CD30 promoter (-413 to 84) induces a 50- to 1000-fold higher luciferase expression in CD30(+) human lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30(-) human carcinoma cell lines (HeLa and MCF-7), or COS1 cells.
Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma.
Clonality detection rates in cHL improved as CD30-positive Reed-Sternberg (RS) cell density increased and CD20-positive B cell density decreased, although these correlations did not reach statistical significance.
A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context.234 CD30+ HL patients were enrolled.
Antitumor immune response of programmed cell death ligand (PD-L1) has shown clinical value not only in Hodgkin lymphoma and EBV-associated lymphomas but also in EBV-negative diffuse large B cell lymphoma (DLBCL) of non-germinal center B cell-like (non-GCB) subtype.
Ets-1, constitutively activated by ERK1/2-MAPK, plays a central role in the overexpression of JunB and CD30, which are both involved in the pathogenesis of HL and ALCL.
<i>In vivo</i>, anti-CD30-MCC-DM1 was found to be capable of inducing tumor regression in subcutaneous inoculation of Karpas 299 (anaplastic large cell lymphoma), HH (cutaneous T-cell lymphoma) and L428 (Hodgkin's disease) cell models.
In lymphoma tissues, autotaxin expression was mainly restricted to CD30+ anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P = .006).
Hodgkin's and many diverse non-Hodgkin's lymphomas overexpress the Hodgkin's disease antigen CD30 (CD30(hi)), a tumor necrosis factor receptor II family member.
The purpose of this article is to review the pathologic and clinical spectrum of ALCL, including the borderline with Hodgkin's disease and lymphomatoid papulosis and to discuss the use of the t(2;5) in better defining a more specific molecular pathologic entity within this group of diseases with CD30 expression.