Intratumoral Microbiome in Soft Tissue Sarcoma Linked to Prognosis

A measurable intratumoral microbiome was identified in soft tissue sarcoma that associates with higher natural killer cell infiltration and improved metastasis-free and overall survival. These findings were published in the Journal for ImmunoTherapy of Cancer.

Research has demonstrated a link between the gut microbiome and immune homeostasis and antitumor immune responses. In this study, researchers explore the possibility of an intratumoral microbiome in soft tissue sarcoma (STS), given the evidence of this type of microbiome across other cancer types such as melanoma and breast, lung, and pancreatic cancers.

A team of researchers at the University of California Davis conducted a prospective cohort study to evaluate intratumoral microbiomes in patients with nonmetastatic STS who were undergoing neoadjuvant radiotherapy (RT) and surgery.

Stool samples and STS tumor samples were procured from participants for microbiome analysis. The stool samples were self-collected before neoadjuvant RT and after RT before surgical resection. Tumor samples were collected at biopsy and from the excised specimen at the time of surgery using a strict sterile tissue collection protocol to minimize the risk of contamination. DNA was isolated in all the specimens and extracted for sequencing.

After analysis, the presence of a measurable intratumor microbiome was demonstrated in patients with STS at diagnosis and after RT using whole genome shotgun sequencing. Furthermore, these findings suggest a prognostic significance in the STS intratumor microbiome at diagnosis, adding that “intratumoral viral relative abundance is linked with intratumoral NK (natural killer) cell infiltration and better survival.”

However, an association between outcomes and the gut microbiome was not observed. This could be the result of the complexity of the microbiome in the gut or because the gut microbiome links more closely to systemic therapies (eg, immune checkpoint inhibitors) than to local therapies (eg, surgery, RT).

“Ultimately, our data demonstrate the presence of a measurable and clinically relevant intratumoral microbiome in a prospective STS cohort,” the researchers concluded. “We demonstrate that among patients with metastatic progression and death, the intratumoral microbiome has prognostic significance and viral relative abundance to drive NK infiltration and better prognosis.”

The small cohort (15 patients) and relatively short follow-up (median 24 months) limit the researchers’ ability to derive robust conclusions regarding potential associations with relapse and survival. Additionally, despite careful preparations, contamination and false positive results tend to be a challenge for microbiome studies.

Reference

Perry LM, Cruz SM, Kleber KT, et al. Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis. J Immunother Cancer. 2023;11(1):e004285. doi:10.1136/jitc-2021-004285