Table 1.
Microbiome profiling of responding vs. non-responding NSCLC patients treated with ICIs.
| References | Sample | Type of Study | ICI | Stage of NSCLC | N | Technique | Responders | Non Responders | Notes | Country |
|---|---|---|---|---|---|---|---|---|---|---|
| (Routy et al., 2018) [22] |
Feces | Retrospective | Anti-PD-1 | All stages | 153 | WGS | Higher: Akkermansia muciniphila, Ruminococcus spp., Allistepes spp. and Eubacterium spp. | Higher: Parabacteroides distasonis, Bacteriodes nordii | ATB uptake negatively impacts OS, but proton pump inhibitor did not. | France |
| (Derosa et al., 2022) [32,33] |
Feces | Prospective | Anti-PD-1 | All stages | 338 | WGS | Higher: A. muciniphila, Eubacterium hallii, and Bifidobacterium adolescentis | Higher: Clostridium innoccuum | Stools with Akkermansia above the 77th percentile is deleterious. | France, Canada |
| (Newsome at al., 2022) [36] |
Feces | Prospective | Anti-PD-1/PD-L1 or anti-PD-L1 and anti-CTLA-4 combination | Advanced | 65 | 16S rRNA (V1-V3) |
Higher: Ruminococcus, Akkermansia, Blautia, and Faecalibacterium | NA | RNAseq on fecal RNA (N = 10) showed different bacterial transcriptomes within responders and non-responders, such as carbon fixation pathway enriched in prokaryotes in responders while non-responders were enriched in phosphotransferase system. | United States |
| (Martini et al., 2022) [38] |
Feces | Prospective | Anti-PD-L1 | Advanced | 10 | 16S rRNA (V4) |
Higher: Agathobacter M104/1 and Blautia SR1/5 | NA | All patients received ICI as cetuximab + avelumab combination. | Italy |
| (Katayama et al., 2019) [39] |
Feces | Retrospective | Anti-PD-1 | Advanced | 17 | 16S rRNA (V1-V2) |
Higher: Lactobacillus, Clostridium, and Syntrophococcus | Higher: Sutterella, Bilophila and Parabacteroides | Patients with higher abundance of Lactobacillus and Clostridium also had longer treatment to TTF. | Japan |
| (Hakozaki et al., 2020) [40] |
Feces | Prospective | Anti-PD-1/PD-L1 | Advanced | 70 | 16S rRNA (V3-V4) | Higher: Agathobacter and Ruminococcaceae UCG 13 | Higher: Eggerthellaceae and Barnesiella | ATB use was associated with lower α-diversity. Lactobacillaceae and Raoultella were enriched in patients with no significant irAE. | Japan |
| (Shoji et al., 2021) [41] |
Feces and Saliva | Prospective | Anti-PD-1/PD-L1 | Stage II/III/IV | 28 | 16S rRNA (V3-V4) |
Higher: Blautia | Higher: RF32 unclassified | Responders had higher α-diversity but lower β-diversity in feces. No significant signal was found from saliva. |
Japan |
| (Ouaknine et al., 2018) [42] |
Blood | Prospective | Anti-PD-1 | Advanced | 35 | 16S rRNA (V3-V4) |
Higher: Peptostreptococcaceae, Lewinella, Paludibaculum, and Holophagae | Higher: Gemmatimonadaceae | Presence of Gemmatimonadaceae at baseline was associated with worse PFS and OS. | France |
| (Jin et al., 2019) [43] |
Feces | Prospective | Anti-PD-1 | Advanced | 37 | 16S rRNA (V3-V4) |
Higher: Alistipes putredinis, Bifidobacterium longum, and Prevotella copri | Higher: Ruminococcus_unclassified | Responders had higher α-diversity. High α-diversity was associated with enhanced memory T cell and NK cell signatures. | China |
| (Song et al., 2020) [44] |
Feces | Prospective | Anti-PD-1 | Advanced | 63 | WGS | Higher: Parabacteroides and Methanobrevibacter | Higher: Veillonella, Selenomonadales, and Negativicutes | Responders had higher β-diversity. Differences in KEGG functional group and metabolic potential of methanol and methane were also noted. | China |
| (He et al., 2021) [45] |
Feces | Prospective | Anti-PD-1 | Advanced | 16 | 16S rRNA (V3-V4) |
Higher: Escherichia, Shigella, Akkermansia, and Olsenella | Higher: Anaeroglobus | Escherichia-Shigella was positively correlated with IL-12, IFN-γ, and basophils in plasma. Akkermansia was positively correlated with monocytes. | China |
| (Zhang et al., 2021) [46] |
Feces and Saliva | Prospective | Anti-PD-1 | Advanced | 75 | 16S rRNA (V3-V4) |
Higher (in feces): Desulfovibrio, Actinomycetales, Bifidobacterium, Odoribacteraceae, Anaerostipes, Rikenellaceae, Faecalibacterium, and Alistipes | Higher (in feces): Fusobacterales, Fusobacteriia, Fusobacterium, Fusobacteria, and Fusobacteriaceae | Responders had higher α-diversity in feces. The abundance of Streptococcus in saliva was associated with higher CD8+ T cell density. α-diversity between feces and saliva microbiota was uncorrelated. | China |
| (Masuhiro et al., 2022) [47] |
BAL | Prospective | PD-1 | Advanced | 12 | 16S rRNA (V3-V4) |
Higher: Bacteriodetes | Higher: Proteobacteria | Responders had higher α-diversity and CXCL9 levels in BAL. | Japan |