Single cell imaging mass spectrometry spatial immune profiling of brain metastasis from non-small-cell lung cancer patients treated with immune checkpoint inhibitors
Year: 2026
Type: article
Study design: Case Report
Abstract: Background: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy is the primary therapy for patients with non-small cell lung cancer (NSCLC) without driver mutations, and brain metastases continue to be a challenge.Methods: Four brain metastasis tissues were available from three patients treated with ICIs, and an eleven-marker panel was stained on formalin-fixed paraffin-embedded (FFPE) slides for imaging mass cytometry (IMC) analysis. Spatial cell count analyses and cell neighborhood analyses were performed to describe the cell population, distribution, and spatial neighborhood in the brain metastasis tumor microenvironment (TME). Given the number of specimens available, no formal statistical comparison between response groups was performed with all analyses done with descriptive statistics and exploratory.Results: In this study, we found enrichment of CD4+FOXP3+ (27.6%), PanCK+CD68+PD-L1+CD33+ (22.7%), and PanCK+PD-L1+CD33+ (15.6%), and weak CD68+ (12.7%) in samples from the patient who exhibited a partial response (PR) to ICIs. In samples from progressive disease (PD) patients, we observed enrichment of PanCK+ (42.5%), weak PanCK+ (28.2%) and Arginase+ (10.7%). In the PR patient with two timepoints, the earlier sample was enriched with neighborhoods 2 and 3, which consist of PanCK+ cell clusters mixed with multiple markers and overlapping T Cells. The later sample was enriched with neighborhood 0 (CD4+FOXP3+) and neighborhood 1 (weak CD68+, and CD8+ T cells), with neighborhood 1 surrounded by neighborhood 0. Weak CD68+ cells were present in both PR and PD patients, but the majority (98.7%) were observed in the single PR patient.Conclusions: We investigated the spatial TME features of brain metastases from NSCLC patients and identified distinct IMC phenotypic profiles, and suggested the potential role for immunosuppressive macrophage and Tregs in ICI resistance mechanisms in brain metastasis. Given the small number of patients, the absence of orthogonal validation and the restricted marker panel, further studies of more samples with comprehensive analysis are required.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223808762