Soluble CD27-Pool in Humans May Contribute to T Cell Activation and Tumor Immunity

Abstract

The interaction between CD27 and its ligand CD70 has been implicated in regulating cellular immune responses to cancer. Here we report on the role of soluble CD27 (sCD27) in T-cell activation and its elevation in the serum of cancer patients after immunotherapy. In vitro, sCD27 is preferentially derived from activated CD4+ T cells. Adding sCD27 to stimulated peripheral blood mononuclear cells increases T-cell activation and proliferation, and is associated with the immunological synapse-related proteins myosin IIA, HMGB1, and the TCR Vβ chain. The pool of serum sCD27 is shown to be greater in healthy donors than in cancer patients. However, metastatic cancer patients treated with immunotherapy showed a significant increase in the serum sCD27-pool post-therapy (p < 0.0005); there was also an increased trend towards an association between enhanced sCD27-pool post-therapy and overall survival (p = 0.022). The identification of sCD27 as an immune modulator associated with enhanced human T-cell activation in vitro and in vivo provides a rationale for developing new immunotherapeutic strategies aimed at enhancing sCD27 for treating cancer and potentially other diseases.

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

“…Both sCD27 (42) and CD70 (8) contribute to T-cell activation and proliferation. However, we could not see any proliferative effects of recombinant sCD27 in response to CD70 in two RCC cell lines (data not shown).…”

CD70: An emerging target in cancer immunotherapy

“…Contrarily to its correlation with outcome in hematological malignancies, no effect on overall survival was found in patients with prostate cancer. Moreover, these patients presented a lower pool of serum sCD27 compared to healthy donors (Huang et al, 2013). Notably, sCD27 did show potential as a prognostic marker in non-small cell lung cancer whereby elevated sCD27 levels correlated with reduced overall survival and progression free survival (Jacobs et al, 2015).…”

Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70

“…CD27 is considered to act as a lymphocyte-specific co-stimulatory molecule via binding to its unique ligand CD70, which is also restricted to activated lymphocytes [18]. Moreover, CD27 can be released as a soluble form called sCD27, thus potentially acting as either agonist or antagonist [18,19]. CLL cells express both cell surface and soluble CD27 [20] and blocking the release of sCD27 using MMP-9 inhibitors induce higher levels of accessory molecules such as CD54, CD80 and CD95 [21].…”