Frontiers in Immunology (Feb 2023)
Specific cannabinoids revive adaptive immunity by reversing immune evasion mechanisms in metastatic tumours
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Christi Wood,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Carola Dreier,
- Carola Dreier,
- Carola Dreier,
- Carola Dreier,
- Carola Dreier,
- Nicolas H. Garcia,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Brett A. Eyford,
- Brett A. Eyford,
- Brett A. Eyford,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Giorgia Caspani,
- Giorgia Caspani,
- Giorgia Caspani,
- Giorgia Caspani,
- Giorgia Caspani,
- Giorgia Caspani,
- Eliana Al Haddad,
- Eliana Al Haddad,
- Eliana Al Haddad,
- Eliana Al Haddad,
- Eliana Al Haddad,
- Eliana Al Haddad,
- Patrick W. Gray,
- Tunc Morova,
- Nathan A. Lack,
- Nathan A. Lack,
- Raymond J. Andersen,
- Larry Tjoelker,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies
Affiliations
- Sarah Dada
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Sarah Dada
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Christi Wood
- Biotechnology - Biomedical Science and Technology (BST), University of Applied Sciences, Mannheim, Germany
- Lilian L. Nohara
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- Biotechnology - Biomedical Science and Technology (BST), University of Applied Sciences, Mannheim, Germany
- Nicolas H. Garcia
- Pascal Biosciences, Seattle, WA, United States
- Iryna Saranchova
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Iryna Saranchova
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Lonna Munro
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Suresh Kari
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Giorgia Caspani
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Giorgia Caspani
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Giorgia Caspani
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Giorgia Caspani
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Giorgia Caspani
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Giorgia Caspani
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Eliana Al Haddad
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Eliana Al Haddad
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Eliana Al Haddad
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Eliana Al Haddad
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Eliana Al Haddad
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Eliana Al Haddad
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Patrick W. Gray
- Pascal Biosciences, Seattle, WA, United States
- Tunc Morova
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Nathan A. Lack
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Nathan A. Lack
- School of Medicine, Koç University, Istanbul, Türkiye
- Raymond J. Andersen
- 0Department of Chemistry, University of British Columbia, Vancouver, BC, Canada
- Larry Tjoelker
- Pascal Biosciences, Seattle, WA, United States
- Wilfred A. Jefferies
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- 1Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- 2Department of Urological Science, University of British Columbia, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fimmu.2022.982082
- Journal volume & issue
-
Vol. 13
Abstract
Emerging cancers are sculpted by neo-Darwinian selection for superior growth and survival but minimal immunogenicity; consequently, metastatic cancers often evolve common genetic and epigenetic signatures to elude immune surveillance. Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery (APM) that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Fascinating ethnographic and experimental findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty. Here, we screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules such as Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in a wide variety of metastatic tumours that subsequently sensitizing tumours to T lymphocyte recognition. Remarkably, H3K27Ac ChIPseq analysis established that cannabigerol and gamma interferon induce overlapping epigenetic signatures and key gene pathways in metastatic tumours related to cellular senescence, as well as APM genes involved in revealing metastatic tumours to the adaptive immune response. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease. Finally, the fundamental discovery of the ability of cannabinoids to alter epigenetic programs may help elucidate many of the pleiotropic medicinal effects of cannabinoids on human physiology.
Keywords
