The Polyvalent Role of CD30 for Cancer Diagnosis and Treatment

Abstract

CD30, also known as TNFRSF8 (tumor necrosis factor receptor superfamily member 8), is a protein receptor that is heavily glycosylated inside the Golgi apparatus, as well as a tumor marker that is found on the surface of specific cells in the body, including certain immune cells and cancer ones. This review aims to shed light on the critical importance of CD30, from its emergence in the cell to its position in diagnosing various diseases, including Hodgkin lymphoma, where it is expressed on Hodgkin and Reed-Sternberg cells, as well as embryonal carcinoma, anaplastic large cell lymphoma (ALCL), and cutaneous T-cell lymphoma (CTCL). In addition to its role in positive diagnosis, targeting CD30 has been a promising approach treating CD30-positive lymphomas, and there is ongoing research into the potential use of CD30-targeted therapies for autoimmune disorders. We aim to elaborate on CD30's roles as a tumor marker, supporting thus the hypothesis that this receptor might be the aim of cytostatic treatment.

Keywords: CD30; Hodgkin lymphoma; anaplastic large cell lymphoma; cancer treatment; embryonal carcinoma; tumor marker.

Figure 1

The CD30 molecule plays a critical role in cell survival by engaging various signaling pathways that confer an advantage to cells with higher CD30 levels. When activated, CD30 forms trimers and sends out signals through tumor necrosis factor receptor-associated proteins (TRAF), specifically TRAF2, TRAF1, and TRAF5, to stimulate nuclear factor-kappa B (NFkB) pathways and thus increase survival chances. CD30 binding initiates signaling through mitogen-activated protein kinase (MAPK) pathways, including ERK1 and ERK2, that activate mitogen-activated protein kinase kinase kinase. This provides cancerous cells with various anti-apoptotic and pro-survival benefits, with JunB acting as a nuclear transcription factor to further support survival while upregulating CD30 expression.

Figure 2

AFM13 (bispecific antibody), targeting both CD30 antigen and CD16A on NK cells, plays an essential role in creating an “immunological synapse”. This interaction leads to activation of NK cells which then release cytotoxic substances like granzyme B and perforin, which result in cell lysis of CD30 positive cells. Brentuximab vedotin targets CD30-positive cells specifically, leading to their receptor internalization. When exposed to intracellular lysozymes, it releases MMAE, which interferes with tubulin formation and triggers cell apoptosis. Furthermore, when an anti-CD30 CAR-T cell binds its target, downstream signaling pathways and costimulatory signals become active, inducing T-cell effector functions including perforin and granzyme release by T cells that leads to their ultimate destruction and demise of CD30-positive cells.