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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Article
Orthopaedic Surgery (2020)

Immunotherapy is the “fourth pillar” of cancer treatment (Nobel Prize in 2018 by Drs. Allison and Honjo).

The gut microbiome has been shown to impact immunotherapy outcomes in cancer. 

In human-to-mouse experiments involving fecal transplantation (FMT), the effect of the gut microbiome on immunotherapy outcomes was observed to be transferable.

Cancer patients who receive antibiotics prior to initiation of immunotherapy may have worse outcomes, which is hypothesized to be due to the negative impact of antibiotics on the gut microbiome.

Microbiota have also been identified in solid tumors of the pancreas and breast—organs that communicate with the outside world.

In a murine model of pancreatic cancer, the intra-tumoral microbiome was shown to promote inhibitory immune pathways, and antibiotic reversed this effect.

    Cover page: Identification and Characterization of an Intra-Tumoral Microbiome in Soft Tissue Sarcomas
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2023)

    Background

    Groundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.

    Methods

    We prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors.

    Results

    Fifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02-0.03%) in all tumors, including Proteobacteria, Bacteroidetes, and Firmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses.

    Conclusions

    We prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.
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