More on the Microbiome

We have recently written extensively on the microbiome and cancer. Science has just published an article reinforcing our summary which is worth the read. Recall that the microbiome is that collection of microorganisms that live inside of our bodies, and without which we would most likely not survive.

As the authors note:

Cancer immunotherapy has become highly successful against an array of distinct hematological and solid metastatic malignancies. Administration of immune checkpoint inhibitors (ICIs) unleashes T lymphocyte–mediated immune responses by suppressing the interaction of T cell inhibitory receptors with their cognate ligands on tumor or stromal cells. The most widely used ICIs are monoclonal antibodies (mAbs) targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1. PD-1 blockade is highly efficacious against advanced melanoma, non–small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Primary resistance, observed in 60 to 70% of cases, has been attributed to low mutational burden, poor intrinsic antigenicity of tumor cells, absence of priming by potentially immunogenic pretreatment with chemo- or radiotherapy , defective antigen presentation during the priming phase, local immunosuppression by extracellular metabolites, and functional exhaustion of tumor-infiltrating lymphocytes. Recent work in mice has highlighted the key role of the gut microbiota in mediating tumor responses to chemotherapeutic agents and immunotherapies targeting PD-L1 or cytotoxic T lymphocyte–associated protein 4 (CTLA-4). Therefore, we explored the possibility that dysbiosis associated with malignant disease or concomitant antibiotic (ATB) use could influence primary resistance to PD-1 blockade in tumor-bearing mice and cancer patients.Initially, we compared the therapeutic efficacy of PD-1 mAb alone or combined with CTLA-4 mAb in mice with established MCA-205 sarcoma and RET melanoma. Mice were reared in specific pathogen–free (SPF) conditions and treated for 14 days with broad-spectrum combination ATB (ampicillin + colistin + streptomycin) or left untreated. ATB treatment significantly compromised the antitumor effects and survival of mice treated with PD-1 mAb alone or in combination with CTLA-4 mAb.

Thus it is critical to deal with many cancers in a holistic manner and not just rely upon  the therapeutic.