Evidence for infection + microbiome dysbiosis as a driver of cancer continues to grow…and grow. An increasing number of tumor microbiomeshave been identified, with tumor gene expression changes often tied to pathogen activity. These findings clarify cancer “root cause” mechanisms, and also have major implications for the success + management of cancer immunotherapy. For example, I suspect that part of the “cytokine storm syndrome” associated with immunotherapy results from the death of tumor-associated pathogens (a herxheimer-type reaction). Here are two of my favorite 2018 studies on infection and cancer:
Lead author: Robert Gallo, University of Maryland
Robert Gallo (who helped discover the HIV virus) is now working on infection in cancer. In this study, he identified a strain of mycoplasma that creates a protein called DnaK. DnaK promotes cancer by interfering w/ host cell DNA-repair + cell death signaling.
Paper highlight: “Our work provides an explanation for how a bacterial infection can trigger a series of events that lead to cancer…the study also provides a mechanisms for how some bacterial infections can interfere with specific cancer drugs”
Lead author: George Miller, New York University School of Medicine
The team identified a distinct and abundant pancreatic microbiome associated with progressive pancreatic cancer. A series of experiments in mice showed this dysbiotic microbiome drove oncogenesis (cancer) by suppressing macrophage differentiation and T cell activity. In addition, targeting this cancer-promoting microbiome with antibiotics protected against oncogenesis, reversed intratumoral immune tolerance, and enabled efficacy for checkpoint-based immunotherapy.
Paper highlight: “These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of [pancreatic ductal adenocarcinoma (PDA)] and that the microbiome has potential as a therapeutic target in the modulation of disease progression.”