Peripheral biomarker & immune monitoring services for oncology clinical trials

Peripheral IDO1 activity and soluble PD-L1 identify resistance-associated signals in a phase II trial

Higher plasma Kyn/Trp ratio and soluble PD-L1 were associated with resistance and poorer clinical outcomes, complementing tumor-level IDO1 and PD1 profiling.

Clinical trial: 47 patients with advanced gastroenteropancreatic neuroendocrine neoplasms were enrolled in the phase II REGOMUNE study, with 42 evaluable for efficacy. The study investigated regorafenib combined with the anti-PD-L1 antibody avelumab.

Peripheral profiling: Baseline plasma Kyn/Trp ratio was measured and used in the study as a surrogate of peripheral IDO1 activity. Plasma proteomics using Olink Target 96 panels assessed immune-related circulating proteins, including soluble PD-L1.

Integrated finding: Higher plasma Kyn/Trp ratio was associated with lower clinical benefit and poorer PFS and OS, and correlated with tumor IDO1 expression. Higher soluble PD-L1 levels were also associated with poorer clinical benefit and survival, supporting the value of integrating peripheral metabolic and proteomic biomarkers with tumor-level profiling.

Circulating cytokines mirror macrophage-associated resistance in gastric cancer

Plasma proteomics combined with tumor profiling linked circulating macrophage-associated cytokines to primary resistance to PD-1/PD-L1 plus antiangiogenic therapy.

Clinical context: Baseline samples from patients with advanced gastric cancer enrolled in the REGOMUNE and REGONIVO studies were analyzed according to treatment response.

Integrated profiling: Plasma proteomics was combined with spatial transcriptomics and multiplex tissue imaging to connect circulating biomarkers with the tumor immune microenvironment.

Finding: Higher circulating CSF-1, IL-4, IL-8 and TWEAK were associated with poorer outcome and with increased M2-like macrophage abundance in tumor tissue.

Baseline plasma L-arginine is associated with ICI outcome

Baseline circulating L-arginine was associated with clinical benefit from immune-checkpoint blockade and linked to the phenotype of circulating myeloid cells.

Clinical cohorts: Plasma L-arginine was assessed in independent ICI-treated cohorts, including a 77-patient discovery cohort and a 296-patient validation cohort.

Integrated peripheral profiling: L-arginine was quantified by ELISA, while matched PBMCs were characterized by multiplex flow cytometry.

Finding: Low baseline L-arginine was independently associated with poorer clinical benefit, PFS and OS, and with increased PD-L1 expression in several circulating myeloid populations.