Bacterial lipopolysaccharide as a negative predictor of adjuvant gemcitabine efficacy in pancreatic cancer
Menée à partir d'échantillons tumoraux prélevés sur 376 patients atteints d'un adénocarcinome canalaire du pancréas puis validée sur 178 patients supplémentaires (durée médiane de suivi : 88 mois), cette étude met en évidence une association entre la présence intratumorale de lipopolysaccharides bactériens et l'inefficacité de la gemcitabine en traitement adjuvant
Adjuvant gemcitabine is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with (aGC) or without (naGC) adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22–2.49, log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23–2.57, log-rank P = .001), but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as negative predictor for adjuvant gemcitabine efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance.
JNCI Cancer Spectrum , article en libre accès, 2021