Definition

CD70 (Cluster of Differentiation 70), a member of the tumor necrosis factor (TNF) superfamily, is a type II transmembrane protein with the ability to regulate the activation, proliferation and differentiation of T cells and B cells, and plays an important role in regulating the immune response. Its ligand is CD27, which binds to its receptor CD27. Under normal circumstances, CD70 is mainly expressed in activated lymphocytes, but in pathological conditions, CD70 can be highly expressed in a variety of tumor cells, and the high expression of CD70 in tumors may suggest that tumors use CD70 to control CD27-expressing tumor infiltration lymphocytes, resulting in immune escape.

CD70 is a potential anti-tumor target, and CD70 protein overexpression or gene amplification is present in a variety of solid tumors and blood cancers, including diffuse large B-cell lymphoma, renal clear cell carcinoma, low-grade glioma, glioblastoma, pleural mesothelioma, and ovarian cancer. In addition, it is an immune checkpoint protein in autoimmune diseases.

Signaling Pathway

CD70 and CD27 are often co-expressed on malignant cells, and after interacting with CD70, the cytoplasmic residues of CD27 bind to TNF receptor Associated Factor (TRAF), such as TRAF2 and TRAF5, thereby activating NF-κB and c-Jun kinase pathways, leading to proliferation, survival, and differentiation. CD70 is transiently expressed on antigen-activated T and B cells and mature dendritic cells, and constituent expression of CD70 has also been found in a unique antigen-presenting cell population located only in the intestinal lamina propria. During normal hematopoietic development, CD70 expression is strictly regulated and activated by the NF-κB and c-Jun pathways guided by TRAF2/5, which play a role in the initiation, survival, and differentiation of immune cell subsets, or can induce apoptosis by activating the caspase pathway through Siva. Reversing the CD70 signaling pathway activates the PI3K/Akt and MEK signaling pathways, thereby regulating cell expansion, differentiation, and effector function.

Fig. 1 The Structure of CD70

Fig. 2 A Schematic View of CD70 Protein and Previously Reported Mutations, B Schematic View of T cell and Antigen

Presenting Cell's (APC) Interaction. C NM_001252.5:c332C Conservation Across Vertebrae (Base G with Gray Underline)

Function

CD70, as a co-stimulatory molecule, plays an important role in the regulation of immune system activation, particularly by improving the activation, proliferation, and survival of T and B cells, resulting in a more effective immune response. CD70 on activated antigen-presenting cells (APCs), including dendritic cells and B cells, binds to CD27 on T lymphocytes and provides co-stimulation signals. The interaction between CD27 and CD70 leads to the recruitment of intracellular adaptor proteins such as TRAF2 and TRAF5, which then activate signaling pathways including NF-κB and JNK pathways. CD27 signaling stimulates naïve CD4+T lymphocytes to differentiate into Th1 cells by activating the transcription factor T-bet.

In addition to its role in T cell activation and proliferation, CD70 also plays a role in the regulation of B cell activation and differentiation. Receptor binding can also cause reverse signaling via CD70. CD70 reverse signaling activates phosphatidylinositol 3 kinase (PI3K) and MAP kinase signaling pathways, leading to activation of various transcription factors and expression of genes involved in cell growth and survival.

CD70 and Diseases

--CD70 and Hematologic Malignancies

CD70 is expressed in a variety of bloodborne tumors, such as gonopoma, leukemia, multiple myeloma, etc. CD70-positive hematogenous malignancies can promote tumor growth by tumor immune escape. TGF-β-induced and pre-existing intratumoral CD70+ memory from B-cell non-Hodgkin's lymphoma (NHL) T (Tm) cells have a depleted phenotype and high levels of programmed death-1 (PD-1) and TIM-3 (T cell immunoglobulin domain and). mucin domain-3). Notably, blocking CD70 can improve the ability of T cells to resist TGF-β, which indicates that CD70 induces the proliferation and depletion of memory effector T cells.

--CD70 and Nephrocytoma

CD70 was highly expressed in renal cell carcinoma, of which clear cell renal cell carcinoma was expressed up to 78%, papillary nephrocytoma accounted for 32%, and normal kidney cells did not express CD70.

--CD70 and Glioma

CD70 expression in GBM is directly involved in promoting aggressive tumor behaviors, such as growth and migration or invasion, and promotes tumor proliferation through immunosuppressive mechanisms that induce apoptosis in T cells. The results of CD70 CAR-T for the treatment of glioma will be described later.

--CD70 and Lung Cancer

CD70 is not expressed in normal lung tissue, is expressed on tumor-infiltrating lymphocytes in primary, recurrent NSCLC and tumor microenvironment, and tumor-infiltrating lymphocytes around CD70+ tumor cells result in more Foxp3 expression and higher CD4/CD8 ratio.

Alpha Lifetech Inc. is dedicated to developing CD70 diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supplying high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial clients.

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