Role of Microbiota in Lung Cancer: Focus on Immune-Checkpoint Inhibition

Lung cancer (LC) represents a global threat, being the deadliest tumor worldwide. A new hope comes from the immune-checkpoint inhibitors (ICIs), a novel therapeutic approach which reactivates the immune system against the cancer cells. ICIs are antibodies targeting the immune checkpoints and triggering T cells to actively recognize and eliminate malignant cells. Despite their demonstrated efficacy within a portion of LC patients, ICIs show some limitations. One is the potential development of resistance to therapy and tumor recurrence over time. The second one consists in the potential manifestation of immune-related adverse events which can be severe or even fatal. The research is currently working at a fast pace to identify novel biomarkers to tackle LC patients who may truly benefit from ICI-based therapy. Among the proposed source of biomarkers, lung and gut microbiota are currently studied. In this review, all of the up-to-date knowledge concerning the relationship occurring between the airways/gastrointestinal microbiota and LC genesis, development, as well as response to ICIs is discussed in depth. The current preclinical and clinical evidence support two main considerations: (1) The microbiota might be a suitable source of novel diagnostic and prognostic LC biomarkers and (2) The microbiota modulation can be a powerful therapeutic strategy to improve the efficacy of ICIs in LC patients. Overall, the microbiota populating the lungs and the intestine represent a novel valuable weapon against LC.