Abstract:
Although co-inhibitory immune checkpoint proteins are primarily involved in promoting cell-cell interactions
that suppress adaptive immunity, especially tumor immunity, the soluble cell-free variants of these molecules are
also detectable in the circulation of cancer patients where they retain immunosuppressive activity. Nevertheless,
little is known about the systemic levels of these soluble co-inhibitory immune checkpoints in patients with
various subtypes of basal cell carcinoma (BCC), which is the most invasive and treatment-resistant type of this
most commonly-occurring malignancy. In the current study, we have measured the systemic concentrations of
five prominent co-inhibitory immune checkpoints, namely CTLA-4, LAG-3, PD-1/PD-L1 and TIM-3, as well as
those of C-reactive protein (CRP) and vitamin D (VD), in a cohort of patients (n = 40) with BCC, relative to those
of a group of control participants, using the combination of multiplex bead array, laser nephelometry and ELISA
technologies, respectively. The median systemic concentrations of CRP and VD were comparable between the
two groups; however, those of all five immune checkpoints were significantly elevated (P = 0.0184 - P = <
0.00001), with those of CTLA-4 and PD-1 being highly correlated (r = 0.87; P < 0.00001). This seemingly novel
finding not only identifies the existence of significant systemic immunosuppression in BCC, but also underscores
the therapeutic promise of immune checkpoint targeted therapy, as well as the potential of these proteins to serve
as prognostic/predictive biomarkers in BCC.
