Baseline multi‐omics signatures could predict therapeutic response to neoadjuvant anti‐PD‐1 immunochemotherapy in non‐small‐cell lung cancer

TL;DR

Baseline gut microbiome and metabolite profiles can predict how well lung cancer patients respond to a specific immunochemotherapy treatment.

Contribution

The study identifies specific microbial and metabolomic signatures that predict response to neoadjuvant anti-PD-1 immunochemotherapy in NSCLC patients.

Findings

MPR patients had higher gut microbial diversity and specific bacterial enrichment at baseline.

Non-MPR patients showed enrichment of Prevotella and higher linoleic acid metabolites.

Microbial and metabolomic models achieved high accuracy in predicting treatment response.

Abstract

Neoadjuvant anti‐programmed cell death 1 (PD‐1) immunochemotherapy has shown promising efficiency in the treatment of early‐stage non‐small‐cell lung cancer (NSCLC), but it has not consistently yielded durable responses. Biomarkers for the prediction of efficacy are warranted.

We performed shotgun metagenomic and plasma/faecal metabolomic studies in 44 NSCLC patients who underwent neoadjuvant tislelizumab plus platinum‐based doublet chemotherapy. Samples were collected at baseline and before surgical resection, and the major pathologic response (MPR) was evaluated.

MPR patients showed a significantly higher gut‐microbial alpha diversity, an enrichment of Ruminococcaceae, Lachnospiraceae and Clostridiales species, and an increased plasma level of tryptophan metabolites at baseline. On the contrary, non‐MPR patients were characterized by enrichment of Prevotella species in faecal samples and higher plasma levels of linoleic acid metabolites. A high predictive accuracy was achieved using a small panel of differential microbial (Clostridium sp. M62/1 and Eisenbergiella tayi) or metabolomic features (linoleic acid, oxindole‐3‐acetic acid and quinolinic acid) with AUCs > .85.

The baseline characteristics of the gut microbiota and plasma metabolites could provide early predictions of the response to neoadjuvant anti‐PD‐1 immunochemotherapy.

NCT05244837.

Baseline metagenomic and metabolomic signatures were significantly associated with the major pathologic response of neoadjuvant anti‐PD‐1 immunochemotherapy.Integrated microbial model (consists of Clostridium sp. M62/1 and Eisenbergiella tayi) and metabolomic model (consists of linoleic acid, oxindole‐3‐acetic acid and quinolinic acid) could provide early predictions of the response.

Baseline metagenomic and metabolomic signatures were significantly associated with the major pathologic response of neoadjuvant anti‐PD‐1 immunochemotherapy.

Integrated microbial model (consists of Clostridium sp. M62/1 and Eisenbergiella tayi) and metabolomic model (consists of linoleic acid, oxindole‐3‐acetic acid and quinolinic acid) could provide early predictions of the response.

Overview of study design. Metagenomic and plasma/fecal metabolomic studies were performed in 44 NSCLC patients who underwent neoadjuvant tislelizumab therapy plus platinum ‐ based doublet chemotherapy.

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