Microbiome and Antitumor Immunity
Based on the most recent estimate of microbes populating the human body, we are made of bacteria at least as much of human cells and they coexist on our body as result of a dynamic equilibrium between Darwinian competition and cooperation. There is a growing appreciation of the role of the microbiome in cancer-related outcomes and our recent work demonstrated that differential bacterial “signatures” exist in the gut of melanoma patients that responded (R) or not (NR) to immunotherapy. Building on the synergy between scientists from different backgrounds to bridge the chasm between the bench and the clinic, our lab is seeking for innovative strategies to improve cancer prevention and response to immunotherapy by manipulating the human microbiome. We are interested in molecular mechanisms that regulate the crosstalk between innate and adaptive immune system in response to modulation of the microbiome, in particular in the gut.
We are generating and integrating multiOMIC datasets and developing new ex vivo and in vivo systems to create:
- Diagnostic tools, that could reveal high-risk subjects or potential R and NR patients, and guide subsequent immune-based therapeutics.
- Personalized interventions, by combining biotic and abiotic formulations to promote cancer prevention or turn NR patients in R.
MOST RELEVANT PUBLICATIONS
Galiè S, Nezi L.* Cracking cancer with engineered skin commensals. Cell Host Microbe 2023.
Sambruni G, Macandog AD, [...] Zeller G, Nezi L*, Schaefer* MH. Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data. Genome Med 2023.
Nava Lauson CB, [...] Nezi L, Manzo T. Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity. Cell Metab 2023.
Tiberti S, Catozzi C, [...] Nezi L* and Manzo T*. Intra-tumoral infiltration of GZMKhigh CD8+ T effector memory cells determines poor clinical outcome in early-stage CRC. Nat Commun 2022.
Manzo T*, [...] Caprioli RM, Greenberg PD, Draetta G and Nezi L*. Accumulation of Long-chain fatty acids in the tumor microenvironment drives dysfunction in intra-pancreatic CD8+ T cells. J Exp Med 2020.
Gopalakrishnan V*, Spencer CN*, Nezi L*, [...] Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018. *Equal contribution.