Frontiers in Immunology (Mar 2024)
A novel type-2 innate lymphoid cell-based immunotherapy for cancer
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Clara Wenjing Xia,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Stephanie Besoiu,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Pablo L. Finkel,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Suresh Kari,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Ladan Fazli,
- Ladan Fazli,
- Martin E. Gleave,
- Martin E. Gleave,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies
Affiliations
- Iryna Saranchova
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Clara Wenjing Xia
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Stephanie Besoiu
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Pablo L. Finkel
- Department of Urologic Sciences, 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
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- The Djavad Mowafaghian Center 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
- Samantha L. S. Ellis
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Suresh Kari
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Ladan Fazli
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Ladan Fazli
- The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
- Martin E. Gleave
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Martin E. Gleave
- The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Michael Smith Laboratories, 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
- Center for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- The Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fimmu.2024.1317522
- Journal volume & issue
-
Vol. 15
Abstract
Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.
Keywords
- cell-based cancer immunotherapy
- type 2 innate lymphoid cells
- ILC2
- interleukin-33
- adoptive cell transfer
- tumor infiltrating lymphocytes
