Abstract

The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.

Highlights

  • Non-small cell lung cancer (NSCLC) is one of the most common and difficult to treat cancers in the world

  • Commensal bacteria play an important role in maintaining the immune homeostasis of various organs and tissues, their balance canthe affect the susceptibility ofvarious the body to Commensal bacteriaand playdisturbances an importantin role in maintaining immune homeostasis of organs and tissues, and disturbances in their balance can affect the susceptibility of the body to carcinogenesis or tumor progression

  • The first part of the study was focused on characteristics of the lung microbiome in NSCLC tumors with different histopathologic features that help gaining insight into the possible role of a microbiome in carcinogenesis or tumor progression

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Summary

Introduction

Non-small cell lung cancer (NSCLC) is one of the most common and difficult to treat cancers in the world. In Russia today, lung cancer ranks first in morbidity and mortality among all types of cancer. Despite the fact that these diseases are well studied, reliable prognostic requirements of this pathology are not convincing enough. One of the new approaches to predict the course and possibly effectiveness of immunotherapy (which is actively used in the treatment of NSCLC) may be a comprehensive analysis of the unique phenotypic characteristics of the tumor stroma, namely the cellular composition of the inflammatory infiltrate together with the composition of its microbiome. The microbiota consists of viruses, bacteria, archaea, protists and fungi, predominant microorganisms in the microbiota of the human respiratory tract are bacteria.

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