Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

Abstract

Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet.In contrast to other tumor entities, sPD-1/sPD-L1 levels did not indicate an adverse outcome in a cohort of 41 patients with advanced PC. We observed a close positive correlation of sPD-L1 levels with sPD-1 in patients with advanced PC, suggesting a common provenience and regulation of sPD-1 and sPD-L1 in cancer patients. Higher sPD-L1 levels were present in patients with elevated C-reactive protein or strong tumoral T cell infiltration, while no correlation of sPD-L1 levels with tumoral PD-L1 expression was found. Our findings indicate that sPD-1 and sPD-L1 are markers of systemic inflammation in (pancreatic) cancer. In a subset of PC patients, elevation in sPD-L1 levels might be caused by an inflammatory tumor typeindependent of tumoral PD-L1 expression.

Senescent cells re‐engineered to express soluble programmed death receptor‐1 for inhibiting programmed death receptor‐1/programmed death ligand‐1 as a vaccination approach against breast cancer

“…20,21 Another possible approach for reversing vaccination failure is to combine sPD-1, which is a soluble form of PD-1 detected in the blood of patients with autoimmune disease (AID), associated with intense inflammation through blockade of the PD-1 suppressive pathway by interaction with PD-L1. 22,23 In the present study, we found that senescent whole-tumor-cell vaccination significantly shifted DC towards maturity followed by Tcell activation in vivo. Moreover, stress-induced senescent cells reengineered to secrete sPD-1 were safer and much more effective than control when vaccinated into mice.…”

“…The clinical effect of blockade has been shown in a number of advanced malignancies . Another possible approach for reversing vaccination failure is to combine sPD‐1, which is a soluble form of PD‐1 detected in the blood of patients with autoimmune disease (AID), associated with intense inflammation through blockade of the PD‐1 suppressive pathway by interaction with PD‐L1 …”

High serum PD‐L1 level is a poor prognostic biomarker in surgically treated esophageal cancer

“…PD‐L1 is mainly expressed in tumor cells; therefore, high concentrations of PD‐L1 represent large tumor volumes and/or highly malignant tumors . On the other hand, several reports have demonstrated no significant associations between tumoral PD‐L1 expression and serum PD‐L1 levels, suggestive of the fact that a high level of serum PD‐L1 might be related to the immunological condition of the patient. Similar to hepatocellular carcinoma and gastric cancer, no associations were noted between serum PD‐L1 levels and tumor stage or tumor size.…”

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

“…Patients with EGFR‐mutated advanced NSCLC who were treated with erlotinib and had a more favorable outcome showed higher expression of sPD‐1 in their blood . In contrast, serum levels of sPD‐1 or sPD‐L1 had no effect (adverse or otherwise) on the overall survival of advanced pancreatic cancer patients, although these levels were indicative of systemic inflammation in pancreatic cancer …”