Loading
Radiomics and Machine Learning in Medical Imaging / Ferroptosis and Cancer Prognosis · Journal article
International Immunopharmacology · August 15, 2026
Encouraging direction, but not yet definitive.
This exploratory study demonstrates an association between pre-treatment ex vivo T cell phospho-signalling in response to pembrolizumab and overall survival in NSCLC patients (HR 2.83, p=0.013), with in vivo T cell differentiation patterns supporting the findings. The authors acknowledge this is a potential biomarker approach requiring independent validation before clinical application and cannot yet guide treatment decisions.
Single-centre exploratory biomarker study with ex vivo immunopharmacological assay and survival analysis. NSCLC patients; peripheral blood mononuclear cells assessed at baseline before treatment.. Intervention: Ex vivo stimulation of PBMCs with anti-CD3/CD28 and pembrolizumab; measurement of phospho-signalling response.. Compared with: PBMCs stimulated with anti-CD3/CD28 alone (without pembrolizumab).. n = 64.
Patients with optimal pembrolizumab-dependent phosphorylation had longer overall survival (HR = 2.83, p = 0.013) versus low modulation Phospho-signalling score differed significantly between two response patterns identified by hierarchical clustering (p < 0.0001) Conventional pharmacodynamic parameters (EC50 for PD-1 occupancy and Emax for IL-2 production) were not associated with clinical outcomes
Conventional pharmacodynamic parameters reported as non-significant but no effect estimates or confidence intervals provided Conventional pharmacodynamic parameters (EC50 for PD-1 occupancy and Emax for IL-2 production) were not associated with clinical outcomes
Clinicians should not yet use this bioassay to guide pembrolizumab treatment decisions, as the authors explicitly state validation in independent cohorts is required before clinical application. The finding is hypothesis-generating and supports further development of functional T cell biomarkers.
A single-centre, exploratory biomarker study with moderate sample size showing an association between ex vivo T cell phospho-signalling and overall survival (HR 2.83, p=0.013), but requiring validation in independent cohorts before clinical application.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should not yet use this bioassay to guide pembrolizumab treatment decisions, as the authors explicitly state validation in independent cohorts is required before clinical application. The finding is hypothesis-generating and supports further development of functional T cell biomarkers.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Immune checkpoint inhibitors (ICIs), targeting the programmed death (ligand)-1 (PD-1/PD-L1) axis, have significantly improved survival in non-small cell lung cancer (NSCLC). Identifying early-response biomarkers is crucial to optimize therapy. We applied a novel ex vivo immunopharmacological bioassay to assess pembrolizumab-dependent T cell signalling in peripheral blood mononuclear cells (PBMCs) from 64 NSCLC patients. PBMCs were stimulated with anti-CD3/CD28 with or without pembrolizumab, and phosphorylation states of PD-1-dependent T cell receptor (TCR) signalling pathways were measured by spectral flow cytometry. A composite signalling score was calculated representing the net pembrolizumab-induced phosphorylation response. Associations with survival outcomes were evaluated using univariate Cox regression. At baseline, hierarchical clustering of phosphorylation profiles identified two distinct response patterns: low and optimal modulation by pembrolizumab. Patients with optimal pembrolizumab-dependent phosphorylation exhibited higher phospho-signalling score outcomes than those with low pathway modulation ( p < 0.0001), and had longer overall survival (HR = 2.83, p = 0.013). Conventional pharmacodynamic parameters, including half-maximal effective concentration (EC 50 ) for PD-1 receptor occupancy and maximum IL-2 production (E max ), were not associated with clinical outcomes. In vivo, patterns of differentiation from naive to terminal effector memory T cells, positive TCR signalling, and controlled activation early on-treatment associated with longer survival (HRs = 0.53–0.70), consistent with our ex vivo findings. We demonstrate that pre-treatment phospho-signalling, in patient T cells ex vivo treated with pembrolizumab, may be associated with clinical outcomes in NSCLC. This functional bioassay represents a potential approach for biomarker development that requires validation in independent cohorts before clinical application and may ultimately contribute to personalised treatment decisions before therapy initiation.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.