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SSO 2022 Press Release – Modulating the Gut Microbiome Stimulates Anti-Tumor Immunity in Cigarette Smoking-driven Cancer Progression

(Dallas—March 10, 2022—3:31 p.m.) — Cigarette smoke induces severe alterations in the gut microbiome and metabolome and can drive cancer tumor progression, but this may allow researchers to develop a novel biological target for smoking-induced tumor growth.  The research was presented by Tejeshwar Jain, MBBS, from the University of Alabama at Birmingham, at the Society of Surgical Oncology 2022 International Conference on Surgical Care.

Cigarette smoke is a major cancer risk factor, however, there is a lack of clinically actionable targets. Dr. Jain sought to evaluate gut microbiome-targeting as a potential therapy against smoking-induced cancer progression.

He randomized mice into two groups—one was exposed to cigarette smoke for four weeks and the control group were exposed to room air.

Dr. Jain analyzed the gut microbiome and metabolome using 16s rRNA sequencing and untargeted LC-MS metabolomics. To confirm the tumorigenic potential of cigarette-smoke exposure gut microbiome, fecal matter from control or cigarette-smoke exposed mice was transplanted into mice followed by subcutaneous pancreatic cancer implantation. Tumors were immunophenotyped by flow cytometry. To evaluate the role of adaptive immune system, Fecal microbiota transplantation experiment was repeated in knockout mice.

Dr. Jain then randomized the mice receive oral gavage with saline or broad-spectrum non-absorbable antibiotics followed by tumor implantation.

The researchers found that cigarette smoke led to significantly altered beta diversity and differential species enrichment of the gut microbiome, while the gut metabolome was also severely dysregulated, dominated by alterations in the arachidonic acid pathway metabolites. FMT from mice exposed to cigarette smoke was sufficient to drive increased tumor growth in recipient mice when compared to control mice. Immunophenotyping of tumors revealed decreased CD8+ T cell as well as increased CD11b+Ly6G+ MDSC infiltration in cigarette-smoke exposed mice. was unable to promote tumor growth in Rag1 KO mice, suggesting that this effect is dependent on a functional adaptive immune system.

“Gut microbiome ablation of mice exposed to cigarette smoking with broad spectrum antibiotics led to inhibition of smoking-induced tumor growth as well stimulation of anti-tumor immunity with increased CD8+ T-cell infiltration and decreased MDSCs,” Dr. Jain reported.

About the Society of Surgical Oncology

The Society of Surgical Oncology is a dynamic global community of cancer surgeons shaping advancements in the profession to deliver the highest quality surgical care for cancer patients. SSO promotes leading-edge research, quality standards and knowledge exchange, connecting cancer surgeons worldwide to continuously improve cancer outcomes. Our highly regarded educational resources, the Society’s clinical journal, Annals of Surgical Oncology and events, including SSO 2022 – International Conference on Surgical Cancer Care, inspire members and spur each cancer surgeon to grow, improve and thrive.

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