I presented a Science paper about how gut microbiome composition may affect response to immunotherapy in an Immunology Journal Club at UAB on November 15th, 2017.
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?
9. Fig. 2: Composition differences in the gut microbiome are
associated with responses to anti-PD1 immunotherapy
LEfSe = linear discriminant analysis of effect size
10.
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
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
Editor's Notes
When activated T cells reach tumors, they can then be functionally inactivated by engagement of programmed cell death 1 (PD-1) with its ligand PD-L1, which is expressed in peripheral tissues and cancers.4,8,9 Therefore, PD-1 functions as a checkpoint of the effector stage of the immune system, which is distinct from the role of CTLA-4 in limiting T-cell activation.10 Two monoclonal antibodies directed against PD-1, pembrolizumab and nivolumab, have shown clinical efficacy in patients with melanom