Cancer associated bacteria in primary and metastatic non-small cell lung cancer

Authors list

Krupa Thakkar Corentin Richard Hongchang Fu Benjamin S Simpson Hongui Cha Marcellus Augustine Alexander Coulton Andrea Castro Selvaraju Veerian Khalid AbdulJabbar Hanyun Zhang Alexandros Hardas Othman Al-Sawaf Arianna Huebner Maise Al-Bakir Takahiro Karasaki Oriol Pich Chris Bailey Yongwoo David Seo Ashish Damania Manoj Chelvanambi Nadim J Ajami David Moore Monika Sivakumar Mark Hill

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Abstract

While the presence of intratumoural microbes has been well described, their role in tumour evolution is unknown. Here we conducted microbial sequencing of 567 samples from non-small cell lung cancer (NSCLC) patients in the TRACERx 421 cohort, spanning matched primary tumour, metastasis and normal adjacent tissue samples. We demonstrate the presence of cancer-associated bacteria shared across multiple primary tumour regions, enriched for common lung pathogens. Using spatially resolved digital histology data in combination with the bacterial load within the tumour, we show that patients with a high bacterial load and low infiltration of lymphocytes have an overall worse survival. Lastly, signature analysis of mutations in the bacterial genome revealed a predominantly endogenous processes contributing to the mutagenesis of intratumoural bacteria in NSCLC. We present a spatially and longitudinally resolved study of the cancer associated bacteriome in lung cancer.