Some interesting science…

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Presentation transcript:

Some interesting science… Chris Parrish St James’s Institute of Oncology

Checkpoint inhibitors Proven efficacy, e.g. 20% of melanoma patients treated with ipilimumab live longer. What separates them from the remaining 80%? Ansell SM et al., NEJM 372; 311-319

Checkpoint inhibition pathways are too straightforward Christopher J. Nirschl and Charles G. Drake, Clin Cancer Res, DOI: 10.1158/1078-0432.CCR-12-1972 Published September 2013

A clue from the side effect profile? Rastogi, P et al., World J Gastroenterol. Apr 14, 2015; 21(14): 4373-4378

CTLA-4 blockade in germ-free mice Differential response to CTLA4 blockade in specific pathogen-free (SPF) mice vs Germ-free mice. Vétizou M et al., Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota Science. 27 Nov 2015. DOI: 10.1126/science.aad1329

Gavage with B. fragilis confers tumoricidal effect Vétizou M et al., Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota Science. 27 Nov 2015. DOI: 10.1126/science.aad1329

‘Identical’ C57BL/6 mice from different facilities After co-habitation Sivan A et al., Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 27 Nov 2015. DOI: 10.1126/science.aac4255

Cohabitation abolishes the difference Sivan A et al., Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 27 Nov 2015. DOI: 10.1126/science.aac4255

Bifidobacterium augments anti-PD-L1 effect Sivan A et al., Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 27 Nov 2015. DOI: 10.1126/science.aac4255

Mice are not humans. Routy et al, 2017: 249 NSCLC, RCC, UC patients 69 of whom had taken antibiotics for routine reasons prior to anti-PD-1 or anti-PD-L1 therapy Routy B et al., Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 02 Nov 2017: DOI: 10.1126/science.aan3706

Akkermansia muciniphilia Routy B et al., Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 02 Nov 2017: DOI: 10.1126/science.aan3706

A more diverse microbiome Gopalakrishnan, V et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 02 Nov 2017: DOI: 10.1126/science.aan4236

A more diverse microbiome, improves response Gopalakrishnan, V et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 02 Nov 2017: DOI: 10.1126/science.aan4236

Summary The diversity of the gut microbiome, and the presence of specific species can dramatically affect the response to cancer immunotherapy treatment. Mediated by anti-tumour T cell responses Microbiomes likely vary by geography and diet Implications: Can avoiding antibiotics whilst on immunotherapy boost response rates? Probiotics? Microbiome transplants? Checkpoint inhibition is even more complicated than you already thought.