Analyzing the gut microbiome in adolescent and young adult patients with melanoma receiving immune checkpoint blockade.

Abstract

9563 Background: Melanoma is the third most common cancer in adolescent and young adults (AYA), a unique cohort defined as patients between 15-39 years of age per the National Cancer Institute. Immune checkpoint inhibitors (ICI) have changed the landscape for advanced melanoma treatment, and the gut microbiota has been shown to remodel the tumor microenvironment to improve ICI efficacy. There is a paucity of research in this cohort, however studies show that AYA patients, in general, have historically not seen the same survival gains as other age groups. Furthermore, literature shows that survival was much worse for AYA's with stage IV melanoma than observed among older adults. Methods: The AYA cohort in this retrospective review is from the 2021 Science publication entitled "Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response". This cohort was matched on a 2:1 basis with older non-AYA patients 50-70 years of age. We controlled for sex, BMI, race, treatment naivety, stage of disease, as well as smoking, drug, and alcohol status. Results: Our AYA cohort of 23 patients is comprised of 15 females, 22 Caucasians, 20 with primary cutaneous melanoma, 12 with stage III at the start of treatment and 11 with stage IV, 17 were BRAF positive, 8 received combined immunotherapy, 20 were treatment naïve, and 11 were responders. We found no difference in alpha or beta diversity in AYA and older non-AYA patients, however alpha diversity increased with age. This is consistent with literature regarding aging gut microbiomes. Furthermore, we noted the most common microbes found between these groups varied considerably. Using differential analyses, we found, for example, a higher abundance of Ruminococcaceae, at the family level, in older non-AYA patients and a higher abundance of Bacteroides stercoris in AYA patients. Literature shows the relative abundance of Ruminococcaceae increased with age and was significantly higher in older patients. Furthermore, Bacteroides stercoris correlates positively with fiber, grain, and vegetable intake. Additionally, Blautia massiliensia, Blautia obeum, and Dorea longicatena were found to be significantly more prevalent (p=0.010, p=0.34, and p=0.035, respectively)) in older non-AYA patients. These species are all known to be obesity biomarkers. Conclusions: We found that the gut microbiota of AYA and older non-AYA melanoma patients differ. Older non-AYA patients have bacterial species associated with negative biomarkers which may be due to an aging gut microbiome. Establishing microbial features in the AYA population can help with microbiome modulation as a therapeutic strategy. Enriching modalities include fecal microbiota transplantation, probiotics, and improving diet as well as fiber intake. Further research should explore if the gut microbiome influences worse outcomes in AYA's with late stage melanoma.