Jourdan Hydol Smith

Introduction:  Melanoma, considered the deadliest form of skin cancer, is characterized by the malignant transformation of melanocytes which are responsible for producing melanin.¹ Current treatments of melanoma include surgical resection through Mohs Surgery, chemotherapy, and targeted therapy through immune checkpoint inhibitors.¹ Given the importance of treatment through targeted immune therapy, several studies have explored various methods of enhancing response to such therapy. One of the most prominent ways through which response is enhanced is through modification of the gut microbiota.² Prior evidence has shown a positive association between gut microbiota changes, and response to anti-PD1 immunotherapy.² Modifying the gut microbiota through prebiotics has shown promising results in the treatment of melanoma.  Methods: C57BL/6 mice with NRAS mutant melanoma were provided with water and prebiotics (3 percent mucin or long-chain inulin).²  For mucin treatment, C57BL/6 mice were provided with water with or without 3 percent mucin every other day starting 14 days prior to YUMM1.5 tumor inoculation. For inulin treatment, C57BL/6 mice were provided with standard chow, standard chow with long-chain inulin, or modified chow, twice weekly starting 14 days prior to YUMM1.5 tumor inoculation.² 16s rRNA amplicon sequencing was used to profile the fecal microbiota of WT C57BL/6 mice before and 14 days after prebiotic feeding and 20 days after tumor cell inoculation.² Sequencing of the amplified 16S V3-V4 region was followed by computational analysis to identify abundance of phylotype groups in inulin and mucin treated mice. ²This was used to identify relative abundance of phylotypes associated with tumor growth.²  Results: Growth of YUMM1.5 tumors that were subcutaneously transplanted in syngeneic C57BL/6 mice showed significant difference in rate of growth, compared to control mice.² After 20 days tumor volume increased approximately 1000 percent in control mice, whereas mice with inulin only had an approximately 500 percent increase in tumor volume after 20 days.² Furthermore, quantification of tumor-infiltrating IFN-g-producing CD4+ T cells showed a significant difference between the control group and inulin group with the inulin group consisting of approximately ten percent more CD4+ T cells.²Co  nclusion: Inulin serves as a prebiotic that alters the composition of the gut microbiota through decreasing and increasing various species of bacteria such as Ruminococcus. ³ Ruminococcus bacteria as part of the gut microbiota, is showed to enhance the effects of anti-PD1 immunotherapy in melanoma patients. Thus, treatment with inulin has a very strong potential in managing and preventing rapid growth of tumors in melanoma patients.

1. Liu Y, Saeed Sheikh M. Melanoma: Molecular Pathogenesis and Therapeutic Management.
2. Li Y, Elmé L, Segota I, Long T, Peterson SN, Ronai EA. Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth. Published online 2020. doi:10.1016/j.celrep.2020.01.035
3. le Bastard Q, Chapelet G, Javaudin F, Lepelletier D, Batard E, Montassier E. The effects of inulin on gut microbial composition: a systematic review of evidence from human studies. European Journal of Clinical Microbiology & Infectious Diseases. 2020;39:403-413. doi:10.1007/s10096-019-03721-w