Project description
Tumour antioxidants and immune suppression
Reactive oxygen species are unstable molecules produced during normal cell metabolism. While excessive levels cause cellular damage, emerging evidence suggests they also play a critical role in activating immune cells against cancer. Some tumours may exploit this by releasing antioxidant enzymes that neutralise these molecules, thereby suppressing immune activity and evading treatment. With the support of the Marie Skłodowska-Curie Actions programme, the TS-ATM project focuses on a potent antioxidant enzyme released by tumour cells that inhibits the cancer-killing capacity of T cells. Researchers will determine how this enzyme disrupts redox signalling in immune cells and test whether its removal sensitises resistant tumours to immunotherapy. Project findings will challenge the assumption that antioxidants are universally beneficial in cancer treatment.
Objective
Oxidative stress promotes genomic instability and oncogenic signaling in cancer, yet antioxidant therapies have largely failed to improve, and in some cases have worsened cancer outcomes. This necessitates a better understanding of how redox dynamics shape not only the biology of cancer cells but their interactions with the host, including the immune system. Reactive oxygen species (ROS) are essential co-factors in T cell activation but whether cancers exploit this vulnerability to suppress T cell immunity and immunotherapy responses is not known. My preliminary data reveal that peroxiredoxin 1 (PRDX1), a potent ROS-scavenging enzyme primarily expressed and released by tumour cells, profoundly inhibit T cell effector function. Genetic deletion of PRDX1 in cancer cells sensitizes otherwise immunotherapy-resistant tumours to checkpoint blockade. I hypothesize that extracellular PRDX1 disrupts redox-sensitive signaling pathways in CD8+ T cells, weakening their cytotoxic capacity and promoting immune evasion of tumours. This hypothesis challenges the prevailing paradigm that antioxidants are inherently beneficial in oncology and instead posits that tumour-derived antioxidants act as immune suppressors. To test my hypothesis, I will pursue three aims: i). Determine whether genetic ablation of PRDX1 in tumours enhances antigen-specific CD8+ T cell responses and improves outcomes following immune checkpoint blockade. ii). Quantify ROS dynamics in T cells across distinct tumour microenvironments and test whether augmenting intracellular ROS levels can overcome T cell suppression. iii). Define the redox-sensitive signaling networks perturbed by PRDX1 and validate key redox signaling mediators in primary human T cells. By uncovering immunomodulatory roles of extracellular antioxidants, this project opens new avenues for understanding immune evasion and offers a transformative strategy to potentiate cancer immunotherapy by reprogramming the tumour redox environment.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology immunotherapy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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CB2 1TN CAMBRIDGE
United Kingdom
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