Thoracic Surgeon; PhD Candidate (Year 4) Fukushima Med. Univ., United States
Disclosure(s):
Sho Inomata, PhD: No financial relationships to disclose
Introduction/Rationale: Non–small cell lung cancer (NSCLC) is the leading cause of cancer death, and robust biomarkers predicting prognosis and/or efficacy of treatment are urgently needed. Tertiary lymphoid structures (TLSs) are recognized as predictors of response to immune checkpoint inhibitors. Tumor-resident bacteria have been shown to promotes TLSs formation. We hypothesized that bacteria in TLSs-high tumors could predict TLSs abundance and ICI responsiveness.
Methods: We reviewed resected cases of lung squamous cell carcinoma (LUSC) from a larger NSCLC cohort collected between 2013 and 2016. Of 39 cases, 24 met prespecified criteria. TLSs status was determined by PNAd⁺ high endothelial venule (HEV) immunohistochemistry. Twelve tumors were classified as TLSs-high and 12 as TLSs-low. Bacterial communities were profiled by 16S rRNA(V3–V4) sequencing and processed with QIIME2/DADA2. Differential taxa were identified with LEfSe (α=0.05, LDA>2.0). Functional profiles were inferred by PICRUSt2 and tested with STAMP (FDR-corrected q < 0.05).
Results: Bacteria specific to the TLS-high group were identified. Genus Ammoniphilus was enriched in TLS-high tumors (7/24; LDA 5.026; p=0.033). Genus Ralstonia was more prevalent in adjacent normal tissues of TLS-high cases (8/24; LDA 4.367; p=0.006). Functional analysis suggested that Ammoniphilus was involved in methionine, nucleotide, and energy metabolism pathways.
Conclusion: We identified Ammoniphilus as a first-in-LUSC candidate microbiome linked to TLSs formation. Its presence could indicate an immunologically “hot” tumor microenvironment and serve as a novel biomarker predicting response to immune checkpoint inhibitors.
