Local tumor microbial signatures and response to checkpoint blockade in non-small cell lung cancer

Boesch, Maximilian; Baty, Florent; Albrich, Werner C.; Flatz, Lukas; Rodriguez, Regulo; Rothschild, Sacha I.; Joerger, Markus; Früh, Martin; Brutsche, Martin

doi:10.1080/2162402x.2021.1988403

Cited by 36 publications

(41 citation statements)

References 56 publications

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“…(1) Tumor microbiome (TM): Although the correlation of the GM and CI outcomes has been well studied, data on the role of the local TM, an important part of the tumor microenvironment, are insufficient. Some studies have explored the correlation between the TM and CI and found the TM can also promote oncogenesis ( 94 ) and affect the treatment effect ( 95 ). The interaction of the TM and the GM influenced the host immune response and tumor growth ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Global research trends on the links between gut microbiota and cancer immunotherapy: A bibliometric analysis (2012-2021)

Yang

Zhao

et al. 2022

Front. Immunol.

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BackgroundThere is a crosstalk between gut microbiota (GM) and cancer immunotherapy (CI). The purpose of this study is to use bibliometric analysis to identify the highly cited papers relating to GM/CI and explore the research status and development trends of the GM/CI research.MethodsA literature search regarding GM/CI publications from 2012 to 2021 was undertaken on July 4, 2022. The article titles, journals, authors, institutions, countries, total citations, keywords, and other information were extracted from the Science Citation Index Expanded (SCIE) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package and VOSviewer were used for bibliometric analysis.ResultsA total of 665 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2018. The United States and China had the most publications and made great contributions to this field. Th5e Univ Texas MD Anderson Canc Ctr and Univ Paris Saclay were absolutely in the leading position in GM/CI. The most influential authors were Zitvogel L and Routy B. Frontiers in Immunology had the most publications and Science had the most total citations. Historical direct citation analysis explained the historical evolution in GM/CI. Highly cited papers and high-frequency keywords illustrated the current status and trends of GM/CI. Four clusters were identified and the important topics included the role of GM and antibiotics in CI, the methods of targeting GM to improve CI outcomes, the mechanism by which GM affects CI and the application of ICIs in melanoma. “Tumor microbiome”, “proton pump inhibitors” and “prognosis” may be the new focus of attention in the next few years.ConclusionThis study filtered global publications on GM/CI correlation and analyzed their bibliometric characteristics, identified the most cited papers in GM/CI, and gained insight into the status, hotspots and trends of global GM/CI research, which may inform researchers and practitioners of future directions.

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Section: Discussionmentioning

confidence: 99%

Global research trends on the links between gut microbiota and cancer immunotherapy: A bibliometric analysis (2012-2021)

Yang

Zhao

et al. 2022

Front. Immunol.

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“…However, local samples can directly modulate NSCLC development and influence the treatment efficacy. For example, local tumor microbial signatures are markers for immunotherapy response in NSCLC ( 5 ). So far, very limited studies have applied different sample types form LC patients to conduct the comprehensive analysis of LM features.…”

Section: Introductionmentioning

confidence: 99%

Lung microbiota features of stage III and IV non-small cell lung cancer patients without lung infection

Zhang¹,

Zhang²,

Han³

et al. 2022

Transl Cancer Res TCR

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Background The microbial community affects the occurrence, development, metastasis and treatment response of cancers. But the detailed role and characteristics of lung microbiota (LM) in non-small cell lung cancer (NSCLC) are not fully known. For NSCLC associated microbiota analysis, it is valuable to combine multiple levels of detection, e.g., tumor, blood plasma, and bronchoalveolar fluid (BALF), but not single tissues. Methods This study collected above three sample types from NSCLC patients free from lung infection and aimed to describe their LM features using sequencing techniques. All patients diagnosed at the Department of Oncology in Shijiazhuang People’s Hospital with stage III or IV NSCLC from May 2019 to April 2020 were enrolled. All 37 pieces of tumor tissues and 6 blood samples were sent for pathogen targeted sequencing; for the BALF samples, 4 were used for pathogen targeted sequencing and 2 were sent for 16S ribosomal DNA (rDNA) sequencing. Results We detected 49 pathogenic microorganisms (PMs) in the 37 tumor samples, 28 PMs in the 4 BALF samples, and 14 PMs in the 6 plasma samples. Overall, there were 5 common PMs in 3 types of samples. Between the tumor and BALF samples, there were another 11 common elements. In the 5 tumor-plasma pairs, the presence of a specific PM in blood was not necessarily consistent with that in the tumor. In the tumor-BALF pairs, the PM diversity was dramatically higher in the BALF than in the tumor. The PMs detected in the BALF could largely cover the PMs in the tumor. In the BALF 16S rDNA sequencing, there were 82 common operational taxonomic units (OTUs), and the microbiota in the BALF of advanced NSCLC patients exhibited some similarity. Conclusions This study showed the unique features of LM. The amount of intra-tumoral PMs was not necessarily consistent with that in the blood, but there was an obvious correlation between the intra-tumoral microbiota and that in the BALF. It is convenient and non-invasive to obtain BALF. Detection of LM classification and abundance in the BALF may help evaluate the severity of NSCLC.

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“…These analyses revealed the consistent presence of bacterial signatures in the samples and suggested high intratumoral abundance especially of Firmicutes, Bacteroidetes, and Proteobacteria. 43 Interestingly, a higher microbial tumor diversity was associated with improved overall survival irrespective of ICI treatment response, indicating treatmentunrelated beneficial effects of tumor microbial diversity in NSCLC patients. 43 Our analyses further showed that high tumorous abundance of Gammaproteobacteria was associated with low PD-L1 expression and poor progressionfree survival (PFS), suggesting that Gammaproteobacteria are preferentially found in PD-L1 low-expressing tumors which typically do not respond well to ICI therapy.…”

Section: Clinical Relevance Of the Tumor-associated Microbiomementioning

confidence: 97%

“…88 Tumor-associated and other tissue microbiomes typically entail a low to very low microbial biomass which can only be investigated using highly sensitive and specific methods. 43 50 55 In the absence of prior knowledge allowing for more targeted investigations, researchers typically aim at dissecting the bulk tumor-associated microbiome (or bacteriome), thus making 'universal species coverage' a top priority. All these criteria are met by modern sequencing-based technologies which have therefore prevailed in the systematic profiling of microbes from clinical samples such as tumor tissue.…”

Section: Techniques and Challenges In Profiling The Tumor-associated ...mentioning

confidence: 99%

Compartmentalization of the host microbiome: how tumor microbiota shapes checkpoint immunotherapy outcome and offers therapeutic prospects

Boesch

Horvath

Baty

et al. 2022

J Immunother Cancer

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The host microbiome is polymorphic, compartmentalized, and composed of distinctive tissue microbiomes. While research in the field of cancer immunotherapy has provided an improved understanding of the interaction with the gastrointestinal microbiome, the significance of the tumor-associated microbiome has only recently been grasped. This article provides a state-of-the-art review about the tumor-associated microbiome and sheds light on how local tumor microbiota shapes anticancer immunity and influences checkpoint immunotherapy outcome. The direct route of interaction between cancer cells, immune cells, and microbiota in the tumor microenvironment is emphasized and advocates a focus on the tumor-associated microbiome in addition to the spatially separated gut compartment. Since the mechanisms underlying checkpoint immunotherapy modulation by tumor-associated microbiota remain largely elusive, future research should dissect the pathways involved and outline strategies to therapeutically modulate microbes and their products within the tumor microenvironment. A more detailed knowledge about the mechanisms governing the composition and functional quality of the tumor microbiome will improve cancer immunotherapy and advance precision medicine for solid tumors.

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Local tumor microbial signatures and response to checkpoint blockade in non-small cell lung cancer

Cited by 36 publications

References 56 publications

Global research trends on the links between gut microbiota and cancer immunotherapy: A bibliometric analysis (2012-2021)

Global research trends on the links between gut microbiota and cancer immunotherapy: A bibliometric analysis (2012-2021)

Lung microbiota features of stage III and IV non-small cell lung cancer patients without lung infection

Compartmentalization of the host microbiome: how tumor microbiota shapes checkpoint immunotherapy outcome and offers therapeutic prospects

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