Novel multiplex immunofluorescence-based tumor inflammation score provides apparent predictive biomarker in a phase I/II study of pembrolizumab with gemcitabine in patients with previously-treated advanced non-small cell lung cancer (NSCLC).
Publication Title
Oncoimmunology
Document Type
Article
Publication Date
12-31-2026
Keywords
Humans; Gemcitabine; Antibodies, Monoclonal, Humanized; Deoxycytidine; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Female; Male; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Tumor Microenvironment; Biomarkers, Tumor; Inflammation; Adult; T-Lymphocytes, Regulatory; Treatment Outcome; Treg/T cell relationship; Tumor microenvironment; antibody response; biomarkers; immune response; multiplex immunofluorescence (mIF); seromics; tumor-associated antigens (TAA).; oregon; chiles; ppmc
Abstract
Retrospective characterization of cell‒cell relationships in the tumor microenvironment provides significantly better predictive power than PD-L1 expression, tumor mutational burden (TMB), or gene expression profiles. In this small study assessing the safety and possible efficacy of gemcitabine and pembrolizumab in immunotherapy-naïve patients with NSCLC who have received prior treatment, we investigated both standard and novel immune parameters in 16 enrolled patients (NCT03083808). The combination of gemcitabine and pembrolizumab could be administered safely but did not demonstrate synergism compared with historical controls. Novel findings of this study are that elevated frequencies of regulatory T cells near CD3 T cells at baseline were associated with improved outcome to treatment (p < 0.05). Integrating this Treg/T cell relationship metric together with overall T-cell density yielded a tumor inflammation score that correlated (p < 0.002) with disease response. We postulate that this is indicative of an ongoing anticancer immune response. Additionally, while prior studies documented that IgG Ab responses to TAA can identify targets of a coordinated T and B cell response and evidence of immune surveillance, this study found that high autoantibody responses, while not statistically significant, trended toward a worse outcome (p = 0.06). This suggests to us that tumors may have developed mechanisms to escape the immune response to these TAAs.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pulmonary Medicine
DOI
10.1080/2162402X.2026.2661444
