Abstract
Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.
Highlights
The gut microbiota (GM) plays a fundamental role in the functional framework of the host immune system and any changes in diet, overuse of antibiotics, xenobiotics and gastrointestinal (GI) tract infections can lead to substantial shifts in the ecology and composition of the individual microbiome over extensive periods [1]
In 2013, science named immunotherapy as a breakthrough in cancer treatment that demonstrated promising results bettering the prognosis of cancer patients across the globe [60,61]
The success was attained through immune checkpoints (ICIs) and chimeric antigen receptor (CAR) T cells [61]
Summary
The gut microbiota (GM) plays a fundamental role in the functional framework of the host immune system and any changes in diet, overuse of antibiotics, xenobiotics and gastrointestinal (GI) tract infections can lead to substantial shifts in the ecology and composition of the individual microbiome over extensive periods [1] Conditions such as immune and inflammatory disorders or induced immunosuppression lead to these shifts, a phenomenon called “dysbiosis” [2]. Proteins like Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed cell death protein 1/Programmed death-ligand 1 (PD-1/PD-L1) have been identified as negative immune regulators or immune checkpoints (ICIs). They are represented as the main targets for immuno-therapeutic interventions. In order to obtain a successful stand in cancer immunotherapy, the therapeutic efforts must be focused on the initiation or re-initiation of the cancer immunity cycle, resulting in an unfettered immune response
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