Summary
Background.
The tumor microenvironment markedly limits intra-tumoral T cell motility and the contact with tumor cells. Such a defective intra-tumoral motility of T cells is one of the main reasons explaining why current treatments based on reinvigoration/infusion of T cells to fight human solid cancers are unsuccessful. Metabolic reactions support T cell migration. Although T cell metabolism is severely de-regulated within different tumor areas, how this specifically affects intra-tumoral T cell motility is unknown. This aspect is important, since the metabolism of tumor-infiltrating T cells could be in principle easily modulated, opening a window of opportunity to improve current immunotherapy approaches against solid cancers, whose ineffectiveness is often associated with a poor intra-tumoral T cell motility.
Objectives.
I want to understand (i) which are the metabolic determinants of T cell motility, (ii) how the metabolic alterations within the TME affect T cell motility, and (iii) how to manipulate the metabolism of T cells and CAR T cells to improve their intra-tumoral motility and anti-cancer response.
Main Methodologies.
Viable tissue slices from human and murine tumors will be used to measure intra-tumoral T cell motility (real-time imaging microscopy) and metabolism (multiparameter imaging approaches, spatial gene expression, histo-cytometry) and to assess the consequences of the manipulation of the metabolic milieu on T cell distribution and motility. Also, CAR T cells will be engineered with new metabolism modules to improve their infiltration into solid tumor.
Expected Results.
The findings of this project will provide new insights into (i) how to improve the metabolic regimen of human solid cancer patients to increase T cell infiltration into tumor islets, and (ii) how to improve the infiltration of CAR T cells during adoptive cell immuno-therapy approaches by modulating their metabolism.
The tumor microenvironment markedly limits intra-tumoral T cell motility and the contact with tumor cells. Such a defective intra-tumoral motility of T cells is one of the main reasons explaining why current treatments based on reinvigoration/infusion of T cells to fight human solid cancers are unsuccessful. Metabolic reactions support T cell migration. Although T cell metabolism is severely de-regulated within different tumor areas, how this specifically affects intra-tumoral T cell motility is unknown. This aspect is important, since the metabolism of tumor-infiltrating T cells could be in principle easily modulated, opening a window of opportunity to improve current immunotherapy approaches against solid cancers, whose ineffectiveness is often associated with a poor intra-tumoral T cell motility.
Objectives.
I want to understand (i) which are the metabolic determinants of T cell motility, (ii) how the metabolic alterations within the TME affect T cell motility, and (iii) how to manipulate the metabolism of T cells and CAR T cells to improve their intra-tumoral motility and anti-cancer response.
Main Methodologies.
Viable tissue slices from human and murine tumors will be used to measure intra-tumoral T cell motility (real-time imaging microscopy) and metabolism (multiparameter imaging approaches, spatial gene expression, histo-cytometry) and to assess the consequences of the manipulation of the metabolic milieu on T cell distribution and motility. Also, CAR T cells will be engineered with new metabolism modules to improve their infiltration into solid tumor.
Expected Results.
The findings of this project will provide new insights into (i) how to improve the metabolic regimen of human solid cancer patients to increase T cell infiltration into tumor islets, and (ii) how to improve the infiltration of CAR T cells during adoptive cell immuno-therapy approaches by modulating their metabolism.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101062302 |
| Start date: | 01-01-2023 |
| End date: | 31-12-2024 |
| Total budget - Public funding: | - 211 754,00 Euro |
Cordis data
Original description
Background.The tumor microenvironment markedly limits intra-tumoral T cell motility and the contact with tumor cells. Such a defective intra-tumoral motility of T cells is one of the main reasons explaining why current treatments based on reinvigoration/infusion of T cells to fight human solid cancers are unsuccessful. Metabolic reactions support T cell migration. Although T cell metabolism is severely de-regulated within different tumor areas, how this specifically affects intra-tumoral T cell motility is unknown. This aspect is important, since the metabolism of tumor-infiltrating T cells could be in principle easily modulated, opening a window of opportunity to improve current immunotherapy approaches against solid cancers, whose ineffectiveness is often associated with a poor intra-tumoral T cell motility.
Objectives.
I want to understand (i) which are the metabolic determinants of T cell motility, (ii) how the metabolic alterations within the TME affect T cell motility, and (iii) how to manipulate the metabolism of T cells and CAR T cells to improve their intra-tumoral motility and anti-cancer response.
Main Methodologies.
Viable tissue slices from human and murine tumors will be used to measure intra-tumoral T cell motility (real-time imaging microscopy) and metabolism (multiparameter imaging approaches, spatial gene expression, histo-cytometry) and to assess the consequences of the manipulation of the metabolic milieu on T cell distribution and motility. Also, CAR T cells will be engineered with new metabolism modules to improve their infiltration into solid tumor.
Expected Results.
The findings of this project will provide new insights into (i) how to improve the metabolic regimen of human solid cancer patients to increase T cell infiltration into tumor islets, and (ii) how to improve the infiltration of CAR T cells during adoptive cell immuno-therapy approaches by modulating their metabolism.
Status
SIGNEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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