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Updated: Jan 10, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Circulating IFNγ-associated protein signatures predict response to neoadjuvant immunotherapy in patients with stage
Fei Yang1,2,3,4, Su Yin Lim1,2, Ines Pires da Silva2,5
1Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
Background:
Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), have transformed the management of stage III melanoma in the neoadjuvant setting. However, a substantial proportion of patients do not derive benefit from ICI therapy. To improve clinical outcomes, there remains a critical unmet need to identify early biomarkers of response to neoadjuvant immunotherapy in stage III melanoma.
Methods:
In this study, we performed longitudinal serum proteomic profiling in 39 patients undergoing neoadjuvant combination anti-PD-1 and anti-CTLA-4 therapy. Using a multiplex proximity extension assay, we measured 702 proteins at three timepoints: baseline, early on-treatment (3-4 weeks after treatment initiation), and pre-surgery (4-8 weeks post-treatment).
Results:
The most pronounced differences between major pathological responders (MPR) and non-MPR patients were detected at baseline and were linked to interferon gamma (IFNγ) signalling, but these differences diminish at later timepoints. A 10-protein IFNγ-associated signature derived from baseline serum profile achieved an AUC of 0.68 for predicting pathological response, comparable to a previously reported tumour-based IFNγ gene signature (AUC = 0.67).
Conclusions:
These findings support the use of circulating protein signatures as minimally invasive, scalable biomarkers to inform early treatment decisions in the neoadjuvant setting.
