The Gut Microbiome Is Associated with Clinical Response to Anti-PD-1/PD-L1 Immunotherapy in Gastrointestinal Cancer
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Peng Z, Cheng S, Kou Y, Wang Z, Jin R, Hu H, Zhang X, Gong JF, Li J, Lu M, Wang X, Zhou J, Lu Z, Zhang Q, Tzeng DTW, Bi D, Tan Y, Shen L
Journal
Cancer immunology research
Year
2020
We report on a comprehensive analysis of the gut microbiomes of patients with gastrointestinal (GI) cancer receiving anti-PD-1/PD-L1 treatment. The human gut microbiota has been associated with clinical responses to anti-PD-1/PD-L1 immunotherapy in melanoma, non-small cell lung cancer, and renal cell carcinoma. We aimed to investigate this association in GI cancers. We also identified bacterial taxa with patient stratification potential. We recruited 74 patients with advanced-stage GI cancer receiving anti-PD-1/PD-L1 treatment and collected their fecal samples prior to and during immunotherapy, along with clinical evaluations. Our 16S rRNA taxonomy survey on the fecal samples revealed an elevation of the Prevotella/Bacteroides ratio in patients, with a preferred response to anti-PD-1/PD-L1 treatment, and a particular subgroup of responders harboring a significantly higher abundance of Prevotella, Ruminococcaceae, and Lachnospiraceae The shotgun metagenomes of the same samples showed that patients exhibiting different responses had differential abundance of pathways related to nucleoside and nucleotide biosynthesis, lipid biosynthesis, sugar metabolism, and fermentation to short-chain fatty acids (SCFA). Gut bacteria that were capable of SCFA production, including Eubacterium, Lactobacillus, and Streptococcus, were positively associated with anti-PD-1/PD-L1 response across different GI cancer types. We further demonstrated that the identified bacterial taxa were predictive of patient stratification in both our cohort and melanoma patients from two previously published studies. Our results thus highlight the impact of gut microbiomes on anti-PD-1/PD-L1 outcomes, at least in a subset of patients with GI cancer, and suggest the potential of the microbiome as a marker for immune-checkpoint blockade responses.See articles by Tomita et al., p. 1236, and Hakozaki et al., p. 1243.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Digestive System Carcinoma carcinoma of digestive system,carcinoma of the gastrointestinal system,digestive system carcinoma,gastrointestinal carcinoma,gastrointestinal carcinoma (disease),gastrointestinal system carcinoma,Digestive System Carcinoma,digestive System Carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders to anti–PD-1/PD-L1 immunotherapy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders to anti–PD-1/PD-L1 immunotherapy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with stage 3 or stage 4 gastrointestinal cancer who achieved an objective response (Partial Responders/Stable Disease) lasting at least 3 months upon treatment start with anti–PD-1/PD-L1 immunotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 29
- Group 1 sample size Number of subjects in the case (exposed) group
- 45
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- centered log-ratio
- Statistical test
- Zero-Inflated Negative Binomial Regression
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3A, Supp. Table S6
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 Immunotherapy in all 74 patients with Gastrointestinal Cancer
Abundance in Group 1: increased abundance in Responders to anti–PD-1/PD-L1 immunotherapy
Revision editor(s): Hamza, Scholastica
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3A, Supp. Table S6
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 Immunotherapy in all 74 patients with Gastrointestinal Cancer
Abundance in Group 1: decreased abundance in Responders to anti–PD-1/PD-L1 immunotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Catenibacterium | ||
| Hungatella | ||
| Ruminococcus_2Ruminococcus_2 | ||
| Ruminococcaceae NK4A214 groupRuminococcaceae NK4A214 group | ||
| uncultured Oscillospiraceae bacterium |
Revision editor(s): Hamza, Scholastica
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-10
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine,Colorectal cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders (colorectal cancer - CRC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (colorectal cancer - CRC)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with colorectal cancer (CRC) who achieved an objective response (Partial Responders/Stable Disease) lasting at least 3 months upon treatment start with anti–PD-1/PD-L1 immunotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 7
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3B, Supp. Table S7
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in patients with Colorectal Cancer (CRC)
Abundance in Group 1: increased abundance in Responders (colorectal cancer - CRC)
Revision editor(s): Scholastica
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3B, Supp. Table S7
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in patients with Colorectal Cancer (CRC)
Abundance in Group 1: decreased abundance in Responders (colorectal cancer - CRC)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Bifidobacterium | ||
| Lachnoclostridium | ||
| Odoribacter | ||
| Oscillibacter | ||
| Parabacteroides | ||
| Subdoligranulum | ||
| Coprococcus_2Coprococcus_2 |
Revision editor(s): Scholastica
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-4-10
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Esophageal carcinoma cancer of esophagus,cancer of oesophagus,cancer of the esophagus,carcinoma of esophagus,carcinoma of oesophagus,carcinoma of the esophagus,esophageal cancer,esophageal cancer, NOS,esophageal carcinoma,esophagus carcinoma,Esophageal carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders (esophageal carcinoma)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (esophageal carcinoma)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with esophageal carcinoma who achieved an objective response (Partial Responders/Stable Disease) lasting at least 3 months upon treatment start with anti–PD-1/PD-L1 immunotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3C, Supp. Table S8
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 Immunotherapy in esophageal carcinoma cancer patients
Abundance in Group 1: increased abundance in Responders (esophageal carcinoma)
Revision editor(s): Scholastica
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3C, Supp. Table S8
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 Immunotherapy in esophageal carcinoma cancer patients
Abundance in Group 1: decreased abundance in Responders (esophageal carcinoma)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Clostridium | ||
| Hungatella | ||
| Lachnospira | ||
| Lactobacillus | ||
| Marvinbryantia | ||
| Ruminococcaceae NK4A214 groupRuminococcaceae NK4A214 group | ||
| uncultured Oscillospiraceae bacterium |
Revision editor(s): Scholastica
Experiment 4
Reviewed Marked as Reviewed by Folakunmi on 2024-4-10
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Gastric cancer Ca body - stomach,ca greater curvature of stomach,Ca lesser curvature - stomach,cancer of stomach,gastric cancer,gastric cancer, intestinal,gastric neoplasm,malignant gastric neoplasm,malignant gastric tumor,malignant neoplasm of body of stomach,malignant neoplasm of lesser curve of stomach,malignant neoplasm of stomach,malignant neoplasm of the stomach,malignant stomach neoplasm,malignant tumor of body of stomach,malignant tumor of greater curve of stomach,malignant tumor of lesser curve of stomach,malignant tumor of stomach,malignant tumor of the stomach,stomach cancer,Gastric cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders (gastric cancer)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders (gastric cancer)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with gastric cancer who achieved an objective response (Partial Responders/Stable Disease) lasting at least 3 months upon treatment start with anti–PD-1/PD-L1 immunotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3D, Supp. Table S9
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in gastric cancer patients
Abundance in Group 1: increased abundance in Responders (gastric cancer)
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella_9Prevotella_9 | ||
| Bifidobacterium | ||
| Prevotella_2Prevotella_2 | ||
| Lachnospira | ||
| Bacteroides | ||
| Ruminococcaceae bacterium UCG-005 | ||
| Agathobacter |
Revision editor(s): Scholastica
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig. 3D, Supp. Table S9
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in gastric cancer patients
Abundance in Group 1: decreased abundance in Responders (gastric cancer)
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Bacteroides | ||
| Bifidobacterium | ||
| Butyricimonas | ||
| Megamonas | ||
| uncultured Lachnospiraceae bacterium |
Revision editor(s): Scholastica
Experiment 5
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Digestive System Carcinoma carcinoma of digestive system,carcinoma of the gastrointestinal system,digestive system carcinoma,gastrointestinal carcinoma,gastrointestinal carcinoma (disease),gastrointestinal system carcinoma,Digestive System Carcinoma,digestive System Carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Responders to anti–PD-1/PD-L1 immunotherapy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-responders to anti–PD-1/PD-L1 immunotherapy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with stage 3 or stage 4 gastrointestinal cancer who did not achieved an objective response (Partial Responders/Stable Disease) lasting at least 3 months upon treatment start with anti–PD-1/PD-L1 immunotherapy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 25
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
Statistical Analysis
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Supp. Table S10
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in patients with Gastrointestinal Cancer (Responders, n=25; Non-responders, n=15)
Abundance in Group 1: increased abundance in Non-responders to anti–PD-1/PD-L1 immunotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Latilactobacillus curvatus | ||
| Catenibacterium mitsuokai | ||
| Dialister succinatiphilus | ||
| unclassified Yersinia (in: enterobacteria) |
Revision editor(s): Scholastica
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Supp. Table S10
Description: Differential abundance between responders and non-responders to Anti–PD-1/PD-L1 immunotherapy in patients with Gastrointestinal Cancer (Responders, n=25; Non-responders, n=15)
Abundance in Group 1: decreased abundance in Non-responders to anti–PD-1/PD-L1 immunotherapy
Revision editor(s): Scholastica
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