Abstract 7619: Tissue-derived peripheral biomarkers that reflect activity of T-cells, macrophages, and neutrophils in patients with solid tumors

Abstract Background: A toolbox of tissue-derived peripheral biomarkers that reflect the activity of T-cells, macrophages and neutrophils is a medical need for immuno-oncology drug development allowing non-invasive quantification of immune cell activity before - and during - treatment, both for predictive and pharmacodynamic purposes. By identifying and quantifying specific extracellular matrix fragments with neo-epitopes that are generated by proteases specific for T-cells, macrophages, and neutrophils, respectively, it is possible to develop peripheral biomarkers that reflect the activity of these immune cells. Such biomarkers have previously shown associations with outcome of patients treated with immune checkpoint inhibitors. Here we investigated the distribution of 3 such biomarkers in different cancer indications. Moreover, these data were compared to data from melanoma patients showing associations with response to cancer immunotherapy. Methods: Tissue-derived biomarkers related to activity of T-cells (C4G: Collagen-4 degraded by Granzyme B), Neutrophils (CPA9-HNE: Calprotectin degraded by neutrophil elastase), Macrophages (VICM: citrullinated and MMP-degraded vimentin) were measured by validated ELISA/ECLIA in serum from patients with various solid tumor types (bladder-, breast- colorectal-, head and neck-, kidney-, lung-, ovarian-, pancreatic, stomach-, prostate- cancer, and melanoma, n=220) and compared to age-matched healthy controls (n=33) by ANOVA. The biomarker levels were compared to historical data. Results: Median biomarker levels of CPA9HNE (neutrophil activity/NETosis) and VICM (macrophage activity) were significantly increased in all solid tumor types (p<0.001), respectively and with a ~5-fold inter-patient variation as well. Median C4G levels was only slightly elevated in a few indications (p<0.05) and with a 5-10-fold inter-patient variation across tumor types. All biomarker levels were independent of disease stage. Similar biomarkers levels were seen to those found to be associated with objective response rate and overall survival of melanoma patients treated with cancer immunotherapy. Conclusion: Tissue-derived peripheral biomarkers that reflect the activity of T-cells (C4G), macrophages (VICM) and neutrophils (CPA9HNE) has biomarker potential in solid tumors and may serve as prognostic, predictive and pharmacodynamic biomarkers in clinical trials investigating cancer immunotherapy. Citation Format: Nicholas Willumsen, Neel I. Nissen, Morten A. Karsdal. Tissue-derived peripheral biomarkers that reflect activity of T-cells, macrophages, and neutrophils in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7619.