The journal club presentation discusses current treatments for advanced melanoma, highlighting targeted therapies and immunotherapies. While targeted therapies show a high response rate of 50-60%, their duration is limited, whereas immunotherapies have lower response rates but significant durability with longer survival outcomes. Additionally, the presentation explores biomarkers, including gut microbiome diversity, that may predict responses to immunotherapy.

1. Journal Club, November 15th, 2017
Presented by Thi Nguyen

2. Passive Non-specific Immunotherapy

3. Current treatments for advanced melanoma
Targeted therapy:
• BRAF or MEK inhibitor, or combination.
• High response rate 50-60%, rapid
• Duration of response is limited, median progression-free survival ~ 6
months.
Immunotherapy:
• Checkpoint inhibitor : anti-CTLA-4 ab (ipilimumab) or anti-PD1
(pembrolizumab)
• Low response rate: 15% for anti-CTLA-4 and 35% for anti-PD1
• Significant durability:
2 year overall survival rate of 60%
4 year overall survival rate of 32%

4. Biomarker assays to predict response to immunotherapy
• PD-L1 (IHC)
• Tumor T cell infiltrate (IHC)
• MDSC, Treg, ICOS+ T cells (Flow)
• Single Cell network profiling
• TCR Clonality (sequencing)
• Mutational load (NGS)
• Microbiome?

6. Fig.1: Microbiome diversity is associated with improved response
N=30 N=13

7. How is Ecological Diversity measured?
• Richness = Number of species/ sample
• Evenness = Relative abundance of different species

8. Fig.1: Microbiome diversity is associated with improved response

9. Fig. 2: Composition differences in the gut microbiome are
associated with responses to anti-PD1 immunotherapy
LEfSe = linear discriminant analysis of effect size

11. Fig.2: Composition differences in the gut microbiome are associated
with responses to anti-PD1 immunotherapy
Metagenomic WGS
R= 14, NR=11
Pairwise comparison
taxa

12. Fig.3: Abundance of crOTUs predicts response

13. Fig.3D: Anabolic pathway enrichment in Responder

14. Fig.4: A favorable gut microbiome is associated with enhanced
systemic and anti-tumor immunity

15. Fig. 4: A favorable gut microbiome is associated with enhanced
systemic and anti-tumor immunity