The role of the lung microbiome in lung cancer.

Seminar Details
Wednesday, March 7, 2018 - 4:00pm to 5:00pm

Speaker

Frank Weinberg, MD, PhD
Second Year Fellow
Division of Hematology and Oncology
Department of Internal Medicine - Michigan Medicine

Location

2813/2817 Med Sci II

Lung cancer is the leading cause of cancer-related death in both men and women in the US. Despite recent advances in treatment of lung cancer, both relapse rates in early stage cancers and overall survival rates in more advanced lung cancer remain poor. Recently, it has been demonstrated that changes in the lung microbiome are associated with chronic diseases such as COPD and Cystic Fibrosis (1). Therefore, it is important to understand the biologic milieu in which lung cancer arises in effort to create more efficacious treatment. Studies demonstrate a shift away from Bacteroidetes phylum, which is a hallmark of the healthy lung, towards Gammaproteobacteria, a class that contains Gram-negative, lung-associated pathogens, in lung disease states (2). A more recent study showed that certain genera of bacteria are enriched for in bronchoalveolar lavage fluid collected from patients with lung cancer versus those with benign mass-like lesions (3).  It was also demonstrated that certain metabolites, like fatty acids, produced by commensal bacteria in the gut can promote the generation of anti-inflammatory regulatory T cells (4). Further studies showed that microbial biofilms from patients with colon cancer produce polyamines which can promote cancer growth and cancer cell transformation (5). Together, these studies implicate a role for local bacterial communities in modulating cancer initiation and progression. Furthermore, in the lung, a recent study showed that commensal microbiota maintain alveolar macrophages which in turn generate cytokines with anti-tumor activity (6). Therefore, understanding the composition of microbial communities and the metabolites they excrete not only will allow for better understanding of the underlying biology of lung tumorigenesis but may offer attractive therapeutic targets as well.

References:

1.         Dickson RP, Erb-Downward JR, Huffnagle GB. The role of the bacterial microbiome in lung disease. Expert Rev Respir Med. 2013;7(3):245-57.

2.         Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol. 2017;10(2):299-306.

3.         Lee SH, Sung JY, Yong D, Chun J, Kim SY, Song JH, et al. Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions. Lung Cancer. 2016;102:89-95.

4.         Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-5.

5.         Johnson CH, Dejea CM, Edler D, Hoang LT, Santidrian AF, Felding BH, et al. Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 2015;21(6):891-7.

6.         Cheng M, Chen Y, Wang L, Chen W, Yang L, Shen G, et al. Commensal microbiota maintains alveolar macrophages with a low level of CCL24 production to generate anti-metastatic tumor activity. Sci Rep. 2017;7(1):7471.