Variation of Plasma Damage-Associated Molecular Patterns in Patients with Advanced Solid Tumors after Standard of Care Systemic Treatment

ABSTRACTBackground Immunogenic cell death (ICD) is known for releasing damage-associated molecular patterns (DAMPs) from tumor cells. We aimed to find ICD signals by assessing the variation of plasmatic DAMPs (HMGB1, S100A8) before-after 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. Plasmatic concentrations of HMGB1 and S100A8 were measured (ng/mL) before and after three months of treatment.Results Fifty-two patients were included. Forty-four patients (85%) had metastases, and 8 (15%) were treated for stage III tumors. The most frequent tumor sites were colorectal (35%) and lung (25%). Forty-two patients (81%) received this treatment in the first-line setting. Thirty-six patients (69%) were treated chemotherapy (CT) alone, ten (19%) CT plus targeted therapy, two (3.8%) carboplatin-pemetrexed-pembrolizumab, three (5.8%) pembrolizumab alone and one (1.9%) cetuximab alone.Median plasmatic concentration of S100A8 was significantly higher before than after treatment in the whole population (3.78 vs. 2.91 ng/mL; P = 0.011) and more markedly in the subgroups of patients who experienced RECIST-assessed tumor response (5.70 vs. 2.63 ng/mL; P = 0.002). Median plasmatic concentration of HMGB1was not significantly different before and after treatment (10.23 vs. 11.85 ng/mL; P = 0.382) and did not differ depending on tumor response.Median PFS was not significantly different between patients whose plasma HMBG1 concentration decreased or increased (8.0 vs. 10.6 months; P = 0.29) after treatment. Median PFS was significantly longer in those patients in whom the plasma concentration of S100A8 decreased after treatment (12 vs. 4.7 months; P < 0.001). Median OS was not significantly different between patients whose plasma HMBG1 concentration decreased or increased (13.1 vs. 14.7 months; P = 0.46) after treatment. Median OS was significantly longer in those patients in whom the plasma concentration of S100A8 decreased after treatment (16.7 vs. 9.0 months; P < 0.001).Conclusions Signals of ICD were not observed. S100A8 behaves as an inflammatory marker with decreased concentration after treatment, mostly in RECIST-responders. PFS and OS were significantly prolonged in those patients who experienced a decrease of S100A8 compared with those patients who experienced increase of plasma S100A8 at three months.KEYWORDS: DAMPssolid tumorssystemic treatmentHMGB1S100A8DisclaimerAs a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also. Additional informationFundingThe Associació Oncológica Dr Amadeu Pelegrí is a charitable organization led by cancer patients, based in Salou (Spain) that provided financial support to perform this study.