Understanding how the intratumoral microbiome affects the efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small-cell lung cancer (NSCLC) is crucial. Preclinical studies suggest that intratumoral Escherichia can create a proinflammatory tumor environment and reduce metastases. This study aims to investigate whether the presence of intratumoral Escherichia impacts the outcome of ICI treatment in NSCLC patients.
The intratumoral microbiome of 958 advanced NSCLC patients treated with ICIs was analyzed using next-generation sequencing reads compared against a bacterial genome database. Environmental contaminants were excluded using no-template controls (n = 2,378). The impact of intratumoral Escherichia on overall survival (OS) was evaluated through univariable and multivariable analyses. Findings were validated in an independent cohort of 772 patients. Additionally, Escherichia fluorescence in situ hybridization (FISH) and transcriptomic profiling were performed.
In the initial cohort, mapping reads to intratumoral Escherichia correlated with significantly longer OS (16 vs. 11 months; hazard ratio, 0.73 [95% CI, 0.59 to 0.92]; P = .0065) in patients receiving single-agent ICI, but not in those undergoing combination chemoimmunotherapy. This association remained significant in multivariable analysis accounting for prognostic factors, including PD-L1 expression (P = .023). The external validation cohort confirmed the improved OS association for single-agent ICI-treated patients but not for those on chemoimmunotherapy. Escherichia localization within tumor cells was validated by FISH staining and serial hematoxylin and eosin sections, while transcriptomic analysis linked Escherichia-positive samples with immune cell infiltration signatures.
The presence of intratumoral Escherichia is associated with improved survival outcomes in NSCLC patients treated with single-agent ICIs. This association was observed in both the discovery and validation cohorts, highlighting the potential of targeting the intratumoral microbiome to enhance ICI efficacy in cancer treatment.
Reference: Arielle Elkrief, Meagan Montesion, Smruthy Sivakumar, Caryn Hale, Anita S. Bowman, Ayyüce Begüm Bektaş, Martina Bradic, Wenfei Kang, Eric Chan, Pooja Gogia, Katia Manova-Todorova, Douglas A. Mata, Jacklynn V. Egger, Hira Rizvi, Nicolas D. Socci, Daniel W. Kelly, Eric Rosiek, Fanli Meng, Grittney Tam, Ning Fan, Alexander Drilon, Helena A. Yu, Gregory J. Riely, Natasha Rekhtman, Álvaro Quintanal Villalonga, Snjezana Dogan, Umesh Bhanot, Mithat Gönen, Brian Loomis, Matthew D. Hellmann, Adam J. Schoenfeld, Marc Ladanyi, Charles M. Rudin, Chad M. Vanderbilt. (July 22, 2024). Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non–Small-Cell Lung Cancer. https://ascopubs.org/doi/abs/10.1200/JCO.23.01488
