Microbiome Meets Melanoma.

"Sivan and colleagues compared genetically identical mice obtained from two different mouse facilities that had different gut microbiota. Interestingly, these mice reacted differently to syngeneic implanted mouse melanoma tumors, apparently because of differences in the vigor of their anti-tumor T-cell responses. These differences were eliminated by cohousing and could be reversed by  fecal transplantation from the mice with anti-tumor immunity, implicating the gut microbiome. Furthermore, fecal transfer augmented responses to anti–PD-L1 immunotherapy. Following sequencing of the bacteria, they found that Bifidobacterium species were overrepresented in mice with better anti-tumor immunity, and introduction of those species into the other mice produced anti-tumor responses. "



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Melanoma Genes Found In "Junk" DNA

US scientists have found two new mutations in non-coding (formerly dubbed "junk") DNA that occur in 71% of malignant melanomas. They say the highly recurrent mutations may be the most common in this deadliest form of skin cancer, more common than the already well-known protein-coding BRAF gene, and may well offer an alternative target for treatment. MNT

Immune-Mediated Regression of Established B16F10 Melanoma by Intratumoral Injection of Attenuated Toxoplasma gondii Protects against Rechallenge.

Immune recognition of tumors can limit cancer development, but antitumor immune responses are often blocked by tumor-mediated immunosuppression. Because microbes or microbial constituents are powerful adjuvants to stimulate immune responses, we evaluated whether intratumoral administration of a highly immunogenic but attenuated parasite could induce rejection of an established poorly immunogenic tumor. We treated intradermal B16F10 murine melanoma by intratumoral injection of an attenuated strain of Toxoplasma gondii (cps) that cannot replicate in vivo and therefore is not infective. The cps treatment stimulated a strong CD8(+) T cell-mediated antitumor immune response in vivo that regressed established primary melanoma. The cps monotherapy rapidly modified the tumor microenvironment, halting tumor growth, and subsequently, as tumor-reactive T cells expanded, the tumors disappeared and rarely returned. The treatment required live cps that could invade cells and also required CD8(+) T cells and NK cells, but did not require CD4(+) T cells. Furthermore, we demonstrate that IL-12, IFN-γ, and the CXCR3-stimulating cytokines are required for full treatment efficacy. The treatment developed systemic antitumor immune activity as well as antitumor immune memory and therefore might have an impact against human metastatic disease. The approach is not specific for either B16F10 or melanoma. Direct intratumoral injection of cps has efficacy against an inducible genetic melanoma model and transplantable lung and ovarian tumors, demonstrating potential for broad clinical use. The combination of efficacy, systemic antitumor immune response, and complete attenuation with no observed host toxicity demonstrates the potential value of this novel cancer therapy.