Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment.

Show less

Author information

Affiliations

  • 1. The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
      Authors
    • Rahal Z 1
    • Lee JJ 1
    • Wang L 1
    • Moghaddam SJ 1
    (4 authors)
  • 2. The University of Texas MD Anderson Cancer Center, United States.
      Authors
    • Liu Y 2
    • Jamal MA 2
    • Sharma M 2
    • Damania AV 2
    • Wong MC 2
    • Tarifa Reischle I 2
    • Chukwuocha C 2
    (7 authors)
  • 3. University of California, Irvine, Irvine, CA, United States.
      Authors
    • Peng F 3
    (1 author)
  • 4. The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
      Authors
    • Yang S 4
    • Sinjab A 4
    • Zhou T 4
    • Feng J 4
    • Leung CH 4
    • Lin HY 4
    • Sepesi B 4
    • Gibbons DL 4
    • Wargo JA 4
    • Kadara H 4
    (10 authors)
  • 5. Baylor College of Medicine, United States.
      Authors
    • Moreno H 5
    • Ross MC 5
    • Hoffman K 5
    (3 authors)
    • Show all (14)

ORCIDs linked to this article

Show all (35)

Cancer Immunology Research, 13 Sep 2024,
https://doi.org/10.1158/2326-6066.cir-24-0469 PMID: 39269772 

Abstract 

Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely associated with tobacco-associated lung adenocarcinoma (LUAD) in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice, exacerbates pro-tumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on LUAD development remains poorly understood. Here, we investigated the role of gut microbiome changes in LUAD development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL-6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with LUAD with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in LUAD and present new potential targets for interception and therapy.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/2326-6066.cir-24-0469

Citations & impact 

Impact metrics

1
Citation
Jump to Citations

Alternative metrics

Altmetric item for https://www.altmetric.com/details/167342294
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/167342294

Article citations

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

NCI NIH HHS (1)

National Cancer Institute (1)