Damage-associated molecular patterns (DAMPS) in patients with advanced cancer undergoing systemic treatment.

Abstract

e14524 Background: Immunogenic cell death (ICD) is known for the release of DAMPS from tumor cells. We aimed to find signals of ICD by assessing the variation of plasma DAMPS (HMGB1 and S100A8) after vs. before standard of care (SoC) systemic treatment in patients with advanced solid tumors. Methods: Patients scheduled to start a new line of systemic treatment were included. Plasma concentrations of HMGB1 and S100A8 were measured (ng/mL) before and after three months of treatment. CD44 immunohistochemical (IHC) expression was determined in tumor tissue. After vs. before variation of paired median concentrations was analyzed with the Wilcoxon signed-rank test for the whole population and selected subgroups according to RECIST response, baseline plasmatic iron levels, CD44 expression, and platinum-based treatment. Results: Fifty-two patients were included. The most frequent tumor sites were colorectal (35%) and lung (25%). Forty-two patients (81%) received this treatment as first-line. Thirty-six patients (69%) received chemotherapy (CT) alone, ten (19%) CT plus targeted therapy (7 FOLFOX or XELOX plus bevacizumab, and one each FOLFOX plus cetuximab, FOLFOX plus panitumumab, docetaxel-trastuzumab-pertuzumab), two (3.8%) carboplatin-pemetrexed-pembrolizumab, three (5.8%) pembrolizumab alone and one (1.9%) cetuximab alone. Overall response rate (RECIST) was 42%, rate of patients with low baseline plasmatic iron levels was 53%, and CD44 expression was positive in 35% of the patients. Results on plasma concentration of DAMPS are shown in the table. Conclusions: Signals of ICD were not observed in these patients. HMGB1 variation was not significant while plasma concentration of S100A8 significantly decreased after treatment, more markedly in those patients who experienced tumor response.[Table: see text]