How the Intratumoral Microbiome Affects Immunotherapy Efficacy in NSCLC

A new study has uncovered an association between overall survival (OS) and intratumoral Escherichia in patients with advanced non-small cell lung cancer (NSCLC) who are receiving single-agent immune checkpoint inhibition.

The large clinical trial, published in the Journal of Clinical Oncology, included 958 patients with advanced NSCLC. Researchers, led by Arielle Elkrief, MD, of the Memorial Sloan Kettering Cancer Center, evaluated unmapped next-generation sequencing reads against a bacterial genome database to determine if intratumoral Escherichia is associated with outcomes in patients receiving immune checkpoint inhibitiors.

“Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases,” the researchers explained.

Overall survival (OS) was the primary endpoint and assessed using univariable and multivariable analyses. An external independent cohort (n=772) was used to further validate the study findings.

Common environmental contaminants were filtered using no-template controls (n=2378). In addition, the researchers also performed fluorescence in situ hybridization (FISH) and transcriptomic profiling for Escherichia.

Study results showed that read mapping to intratumoral Escherichia was associated with an OS of 16 months in patients treated with single-agent immunotherapy compared with 11 months for those who received combination chemoimmunotherapy (P=.0065).

The association with OS in the single-agent cohort remained statistically significant in a multivariable analysis that adjusted for prognostic features, such as PD-L1 expression (P = .023), according to the study authors.

The association with improved OS in univariable and multivariable analyses of patients who received treatment with single-agent immune checkpoint inhibitor was confirmed by the analysis of the external validation cohort.

“Escherichia localization within tumor cells was supported by coregistration of FISH staining and serial hematoxylin and eosin sections,” Dr. Elkrief and colleagues explained. “Transcriptomic analysis correlated Escherichia-positive samples with expression signatures of immune cell infiltration.”

The study highlights the possibility of targeting the intratumoral microbiome to enhance efficacy of treatment with immune checkpoint inhibitors in NSCLC.

Source: Journal of Clinical Oncology