Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome.

The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

Detailed Characterization of the Lung-Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients.

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of ß-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).

MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.

OBJECTIVE: In this study, we determined whether Helicobacter pylori (H. pylori) infection dampens the efficacy of cancer immunotherapies. DESIGN: Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori-infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). RESULTS: In mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8+ T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8+ T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. CONCLUSION: Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment.

Commensal microbiota contributes to predicting the response to immune checkpoint inhibitors in non-small-cell lung cancer patients.

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death-1/programmed cell death-ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non-small-cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes' signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti-programmed cell death-1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression-free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor-based immunotherapy.

Gut Microbiota in Lung Cancer: Where Do We Stand?

The gut microbiota (GM) is considered to constitute a powerful "organ" capable of influencing the majority of the metabolic, nutritional, physiological, and immunological processes of the human body. To date, five microbial-mediated mechanisms have been revealed that either endorse or inhibit tumorigenesis. Although the gastrointestinal and respiratory tracts are distant physically, they have common embryonic origin and similarity in structure. The lung microbiota is far less understood, and it is suggested that the crosslink between the human microbiome and lung cancer is a complex, multifactorial relationship. Several pathways linking their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Regarding implications of specific GM in lung cancer therapy, a few studies showed that the GM considerably affects immune checkpoint inhibitor (ICI) therapy by altering the differentiation of regulatory T cells and thus resulting in changes in immunomodulation mechanisms, as discovered by assessing drug metabolism directly and by assessing the host immune modulation response. Additionally, the GM may increase the efficacy of chemotherapeutic treatment in lung cancer. The mechanism underlying the role of the GLA in the pathogenesis and progression of lung cancer and its capability for diagnosis, manipulation, and treatment need to be further explored.

Characterisation of microbiota in saliva, bronchoalveolar lavage fluid, non-malignant, peritumoural and tumour tissue in non-small cell lung cancer patients: a cross-sectional clinical trial.

BACKGROUND: While well-characterised on its molecular base, non-small cell lung cancer (NSCLC) and its interaction with local microbiota remains scarcely explored. Moreover, current studies vary in source of lung microbiota, from bronchoalveolar lavage fluid (BAL) to tissue, introducing potentially differing results. Therefore, the objective of this study was to provide detailed characterisation of the oral and multi-source lung microbiota of direct interest in lung cancer research. Since lung tumours in lower lobes (LL) have been associated with decreased survival, characteristics of the microbiota in upper (UL) and lower tumour lobes have also been examined. METHODS: Using 16S rRNA gene sequencing technology, we analysed microbiota in saliva, BAL (obtained directly on excised lobe), non-malignant, peritumoural and tumour tissue from 18 NSCLC patients eligible for surgical treatment. Detailed taxonomy, diversity and core members were provided for each microbiota, with analysis of differential abundance on all taxonomical levels (zero-inflated binomial general linear model with Benjamini-Hochberg correction), between samples and lobe locations. RESULTS: Diversity and differential abundance analysis showed clear separation of oral and lung microbiota, but more importantly, of BAL and lung tissue microbiota. Phylum Proteobacteria dominated tissue samples, while Firmicutes was more abundant in BAL and saliva (with class Clostridia and Bacilli, respectively). However, all samples showed increased abundance of phylum Firmicutes in LL, with decrease in Proteobacteria. Also, clades Actinobacteria and Flavobacteriia showed inverse abundance between BAL and extratumoural tissues depending on the lobe location. While tumour microbiota seemed the least affected by location, peritumoural tissue showed the highest susceptibility with markedly increased similarity to BAL microbiota in UL. Differences between the three lung tissues were however very limited. CONCLUSIONS: Our results confirm that BAL harbours unique lung microbiota and emphasise the importance of the sample choice for lung microbiota analysis. Further, limited differences between the tissues indicate that different local tumour-related factors, such as tumour type, stage or associated immunity, might be the ones responsible for microbiota-shaping effect. Finally, the "shift" towards Firmicutes in LL might be a sign of increased pathogenicity, as suggested in similar malignancies, and connected to worse prognosis of the LL tumours. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03068663. Registered February 27, 2017.

The association between gut butyrate-producing bacteria and non-small-cell lung cancer.

BACKGROUND: Recently, it has been found that the gut microbiota may affect the development of lung cancer through the "gut-lung axis." To investigate this relationship, we performed this study to determine whether the gut microbiota in non-small-cell lung cancer (NSCLC) patients is different from that in healthy adults. METHODS: Quantitative PCR (qPCR) was used to detect the expression levels of eight gut butyrate-producing bacteria in healthy adults and NSCLC patients. We enrolled 30 patients with NSCLC and 30 subjects from 100 healthy adults after matching for age and sex. RESULTS: Compared to healthy adults, most of the gut butyrate-producing bacteria in NSCLC patients were significantly decreased; these included Faecalibacterium prausnitzii, Clostridium leptum, Clostridial cluster I, Ruminococcus spp., Clostridial Cluster XIVa, and Roseburia spp. Among the gut butyrate-producing bacteria, we analyzed Clostridial cluster IV and Eubacterium rectale were not decreased in NSCLC patients. CONCLUSIONS: We conclude that NSCLC patients had gut butyrate-producing bacteria dysbiosis. Further studies should be performed to investigate the underlying mechanisms of how these specific bacteria affect lung cancer progression and prognosis.

Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients' prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.

Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer.

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

[Clinical characteristics and microbiome analysis in patients with anti-programmed cell death protein 1 related colitis].

Objective: To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis. Methods: Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse. Results: The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutes decreased with Bacteroidetes increasing in phylum level; while the Bacteroides increased with Ruminococcaceae decreasing in genus level. Lactobacillus was the potentially beneficial genus. Conclusion: Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

Bordetella bronchiseptica pneumonia in a patient with lung cancer; a case report of a rare infection.

BACKGROUND: Bordetella bronchiseptica (B.bronchiseptica) is a frequent cause of respiratory infections in animals but rarely causes serious infection in humans. We present a rare case of B. bronchiseptica pneumonia in a patient with lung cancer. CASE PRESENTATION: A 52-year-old white male with non small cell lung cancer developed fever during treatment with nivolumab. A persistent productive cough and a deterioration in his clinical condition led to his hospitalization for evaluation. Bronchoscopy was performed and a diagnosis of B. bronchiseptica pneumonia was made. The infection was successfully managed by antiobiotic therapy. CONCLUSIONS: B. bronchiseptica is a pathogen that can cause serious infection in humans, especially in immunocompromised or immunoincompetent individuals. In our patient it showed unusual resistance to cephalosporins and poor sensitivity to amikacin. To our knowledge this is the first case of such an infection in a lung cancer patient undergoing treatment with nivolumab. When B. bronchiseptica is identified, the possibility of a nosocomial transmission must be considered.

Methicillin-Resistant Staphylococcus Aureus infection exacerbates NSCLC cell metastasis by up-regulating TLR4/MyD88 pathway.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major public health problem worldwide, which brings to a more great threat for cancer patients. It's necessary to give attentions to lung cancer combined with MRSA. This study mainly focuses on the influences of MRSA on lung cancer cells (A549). We first found that MRSA infection can enhance metastasis ability of A549 cell and increase matrix metalloproteinase (MMP2 and MMP9) expressions in MRSA-infected A549 cell. Toll-like receptors (TLRs) have been reported to play an important role in tumor cell initiation and migration, and regulate the expression of MMPs in tumors. Our further research indicates that Toll-like receptor 4 (TLR4)/molecules myeloid differentiation factor 88 (MyD88) signaling was up-regulated in MRSA-infected A549 cell. After silencing TLR4 or MyD88 gene, the enhanced metastasis ability of A549 cell by MRSA was decreased significantly; Also, MMP2 and MMP9 expression increase was reversed. In conclusion, MRSA infection can enhance NSCLC cell metastasis by up-regulating TLR4/MyD88 signaling.

Does Every Necrotizing Granulomatous Inflammation Identified by NSCLC Resection Material Require Treatment?

BACKGROUND Lung cancer and tuberculosis (TB) are two major public health problems. They can coexist or appear sequentially. In patients with TB, lung cancer risk is increased. However, vice versa is not crystal clear. In this study, we aimed to determine the development of TB in patients with resectabled non-small cell lung cancer (NSCLC) in a 2-year postoperative follow-up period. MATERIAL AND METHODS We conducted a retrospective cohort study at three university hospitals. Patients who had NSCLC surgery between 2009 and 2013 were included and patient records were reviewed for the presence of necrotizing granulomatous inflammation (NGI) in resected specimens. Demographic properties, tumor type, stage, location, type of surgery, tuberculosis history, and thorax CT findings were recorded. We searched for the development of tuberculosis within a 2-year period after surgery. RESULTS A total of 1027 patient cases were reviewed, of which 48 patients had NGI. The median age was 63 years. The most common type of cancer was squamous carcinoma; and lobectomy was the preferred operation (70.8%). Cancer involvement most commonly included the right lung (61.8%) and upper lobes (47,9%). Only 11 patients had anti-TB treatment postoperatively, which was based on radiological findings. Prior tuberculosis or anti-TB history, type, stage or localization of cancer, and adjuvant/neoadjuvant therapy were not found to be related to TB treatment. None of the study population had TB during the two-year follow-up period. Treatment decisions appeared mostly related to physician experience. There was no difference in the risk of developing TB between patients with or without treatment. This finding may change the management of our patients. CONCLUSIONS Every NGI discovered in NSCLC resected material does not always require anti-TB treatment.

Porphyromonas bronchialis sp. nov. Isolated from Intraoperative Bronchial Fluids of a Patient with Non-Small Cell Lung Cancer.

Porphyromonas strains, including Porphyromonas-like strains, have been isolated from oral and various other systemic infections. The characterization of such strains is a crucial issue, because such information contributes to both the taxonomy of anaerobic bacteria and the clinical aspects of infectious diseases. We previously isolated four Porphyromonas-like strains from intraoperative bronchial fluids of a patient with non-small cell lung cancer. This study aimed to characterize the genetic, biochemical and chemotaxonomic aspects of these isolates. Each strain only grew under anaerobic conditions and their colony morphology was convex, 0.1-1.0 mm in diameter, light gray, and slightly glistening colony, with no black or brown pigmentation on blood agar plates after five-day incubation. The pigmentation was helpful to differentiate the isolates from other Porphyromonas, as most of Porphyromonas species show the pigmentation. In the 16S rRNA gene phylogenetic analysis (98% sequence identity of isolates indicates the same species), the four isolates were closely related to one another (99.7-100.0%), but not related to Porphyromonas (P.) catoniae, the closest species (96.9%). In addition, the DNA-DNA hybridization data revealed less than 16% similarity values between a representative isolate and the P. catoniae, indicating that the strains were genetically independent. Biochemically, the isolates could be differentiated from closely related species, i.e., P. catoniae, P. gingivalis, P. gulae, and P. pogonae, with trypsin activity (negative only in the isolates) and leucine arylamidase activity (positive only in the isolates). We therefore propose a new species to include these isolates: Porphyromonas bronchialis sp. nov.

Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.

Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).

Microbiota Diversity in Non-Small Cell Lung Cancer Gut and Mouth Cavity Microbiota Diversity in Non-Small Cell Lung Cancer Patients.

Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.

Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients.

Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.

Characteristics of pathogenic microbes in lung microenvironment of lung cancer patients without respiratory infection.

PURPOSE: The characteristics of pathogenic microbes are useful for understanding the microbe-driven tumorigenesis. There is a lack of studies on the lung microecology for lung cancer (LC) patients without any respiratory infection. In this work, we aimed to describe the profiles of pathogenic microbes in lung microenvironment of non-small cell lung cancer (NSCLC) patients using pathogen targeted sequencing and 16S rDNA sequencing. METHODS: A total of 22 NSCLC patients (13 adenocarcinomas and 9 squamous cell carcinomas) without any pulmonary infection were enrolled. Among them, we collected 15 pieces of tumor tissues, 5 pieces of peritumoral tissues, 6 blood serum samples, and 5 broncho-alveolar lavage fluid (BALF) samples. Pathogen targeted sequencingand16S rDNA sequencing was performed for microbial classification. RESULTS: The pathogen targeted sequencing results showed that 33, 14, 11, and 27 pathogenic microorganisms were detected in tumor tissues, peritumoral tissues, blood samples, and BALF, respectively. No common microorganisms were shared by four sample types. However, some common elements were shared by three sets: Streptococcus cristatus, Enterococcus, Staphylococcus haemolyticus, Corynebacterium pseudodiphtheria, Acinetobacter jungii, Haemophilus haemolyticus and Haemophilus parainfluenzae. Based on the 16S rDNA sequencing of two BALF samples, there were 104 OTUs found in one BALF sample and 127 OTUs in the other BALF sample; among them, there were 82 common ones, such as OTU1, OTU10, OTU101, OTU105, OTU106, and so on. Based on the above microbial classification and abundance, there might be enriched function in COG terms like COG1132, COG0438 and COG0745, and KEGG terms like K06147, K02029, and K09687. CONCLUSION: This study emphasizes the role of the microbiome in LC patients without respiratory infection. These potential biomarkers of LC based on the taxonomic composition of pathogenic microorganisms might have clinical application.

Non-small cell lung cancer microbiota characterization: Prevalence of enteric and potentially pathogenic bacteria in cancer tissues.

Following recent findings linking the human gut microbiota to gastrointestinal cancer and its treatment, the plausible relationship between lung microbiota and pulmonary cancer is explored. This study aims at characterizing the intratumoral and adjacent healthy tissue microbiota by applying a 16S rRNA gene amplicon sequencing protocol to tissue samples of 29 non-small cancer patients. Emphasis was put on contaminant management and a comprehensive comparison of bacterial composition between cancerous and healthy adjacent tissues of lung adenocarcinoma and squamous cell carcinoma is provided. A variable degree of similarity between the two tissues of a same patient was observed. Each patient seems to possess its own bacterial signature. The two types of cancer tissue do not have a distinct bacterial profile that is shared by every patient. In addition, enteric, potentially pathogenic and pro-inflammatory bacteria were more frequently found in cancer than healthy tissue. This work brings insights into the dynamic of bacterial communities in lung cancer and provides prospective data for more targeted studies.