Work

424 Tumour-homing T cells in the blood predict the efficacy of anti-PD-1 immunotherapy in melanoma patients

Year: 2026

Type: conference-abstract

Abstract: Background T cell-mediated control of solid tumours depends entirely on the directed entry, or homing, of circulating T cells into tumour tissues. The first – and thus rate-limiting – step in this process is vascular rolling, primarily mediated by the binding of E-selectin on vascular endothelial cells to the CD15s glycan (sialyl-Lewis X) displayed on the T cell surface. Yet despite its biological importance, it is unknown whether differences in this adhesion axis underpin divergent clinical outcomes to anti-PD-1 immunotherapy.Methods Pre-treatment blood samples were collected from metastatic melanoma patients prior to receiving anti-PD-1 treatment (n = 50 across two clinical sites), with T cells being analysed by high-dimensional flow cytometry and ligand binding assays. In parallel, patient responses to treatment were monitored via radiologic imaging and survival studies. Tumour tissues from a subset of patients were used in multispectral immunofluorescence imaging and high-parameter flow cytometry to characterise intra-tumour T cells and blood vessels. Finally, matched samples of fresh tumour tissue and blood were analysed using single cell transcriptomics and TCR sequencing to assess the clonal relationship between T cells from the two sources.Results We reveal that co-expression of CD15s and the proliferation marker Ki67 identifies a rare subset of blood CD8 T cells that strongly associates with improved radiologic response and overall survival following anti-PD-1 treatment in melanoma patients. This link was observed in two distinct cohorts recruited from different sites, yielding AUC values of 0.81 and 0.77 respectively, but was not observed for other molecules involved in T cell homing, including chemokine receptors and integrins. Spatial analyses of tumour tissue also revealed heterogeneous vascular expression of E-selectin, which similarly associated with anti-PD-1 responsiveness. High-dimensional flow cytometry revealed that the CD15s + CD8 T cell subset in blood is enriched in a progenitor-exhausted phenotype and displays enhanced binding to E-selectin, in keeping with tumour-homing potential. Indeed, we observed that CD15s expression on circulating CD8 T cells correlates with tumour-infiltrating T cell density in matched tissues, and these blood-borne cells show an overlap with TCR clonotypes present in the tumour, directly supporting a tumour-homing function.Conclusions These findings reveal a pivotal role for the CD15s/E-selectin adhesion axis in driving T cells tumour homing activity and anti-PD-1 responsiveness in melanoma patients and provide a tractable approach to guide personalised treatment decisions.Ethics Approval Collection of blood and tissue samples and clinical data was approved by the Central Adelaide Local Health Network HREC (project R20151164) and Peter MacCallum Centre HREC (approval numbers 16/153, 07/38, 11/105 and 16/153). All patients provided informed written consent.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.0424