Under normal physiological conditions, CD27, a member of the tumor necrosis factor receptor (TNFR) superfamily, plays a co-stimulatory role in promoting T cell expansion and differentiation through activation of the NFκB pathway. Consequently, expression of its ligand, CD70, is tightly regulated and only transiently expressed on activated T cells, B cells and mature dendritic cells. In contrast to a total lack of constitutive CD70 expression in normal tissue, CD70 overexpression has been documented in diverse cancer types such as renal cell carcinoma, glioblastoma, and hematological malignancies. In the latter, CD70 overexpression has even been implicated in cancer cell proliferation and survival mediated through its interaction with CD27. Moreover, Claus et al. demonstrated evasion of immune surveillance by recruitment of CD27+ regulatory T cells (Treg) to the tumor site. Consequently, this surface factor might be an interesting and specific therapeutic target in addition to its role as prognostic biomarker. Furthermore, upon binding of CD70 to CD27, soluble CD27 (sCD27) is cleaved off by metalloproteinases and has been detected in serum, plasma, and urine samples from healthy individuals, and at increased levels in patients with autoimmune diseases. In fact, increased levels of sCD27 have been reported to correlate with poor prognosis in various hematological malignancies. Therefore, this study was designed to evaluate the potential use of sCD27 as a diagnostic biomarker for prognosis in solid cancers.
Jacobs J, Zwaenepoel K, Rolfo C, et al. Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer. Oncotarget. 2015;6(15):13462-13475.