Intratumoral microbiome is associated with the response to cancer immunotherapy in lung cancer patients with high...

High expression of tumoral programmed death-ligand 1 (PD-L1) [high PD-L1 tumor proportion score (TPS)] is a predictive biomarker of response to cancer immunotherapy in lung cancer; however, its predictiveness is insufficient. Recently, resident microbiomes in several organs including the lung have been demonstrated to control host immunity but their role in the response to cancer immunotherapy is still unknown.

This single-center, retrospective study analyzed 32 high PD-L1-TPS lung cancer patients treated with immune checkpoint inhibitors (ICI). We carried out shotgun metagenome sequencing using frozen tumor tissues, then analyzed the correlation between the intratumoral microbiota and response to ICI therapy.

In this study, only 56.3% of patients with high PD-L1-TPS showed response to ICI therapy. Among 11 significant compositional differences in intratumoral microbiota observed in ICI responders, there was significantly longer progression-free survival (PFS) in patients with abundant Tetrasphaera and Mesorhizobium. Of patients with these abundant microbiota, 83.3% showed response to ICI therapy and all patients without these microbiota were ICI nonresponders (P = 0.0050). There were significant differences among three groups classified by the abundance of g_Tetrasphaera and g_Mesorhizobium (PFS, P = 0.0016 and overall survival, P = 0.0013). Twenty pathway modules were enriched in ICI responders and eight were enriched in ICI nonresponders.

This study revealed the specific compositions of intratumoral microbiota as demonstrating relevance to response to ICI therapy in high PD-L1-TPS lung cancer patients. The intratumoral microbiota components Tetrasphaera and Mesorhizobium may have a key role in determining the response to cancer immunotherapy for lung cancer.