Project description
Breaking barriers to efficient cancer immunotherapy
In the last few decades, new immunotherapy treatments for cancer have been tested, and new ways to activate the immune system have been discovered at a fast pace. However, many types of cancer are non-responsive to these new treatments. Pre-existing and adaptive resistance mechanisms circumvent the activation of tumour-reactive cytotoxic T cells capable of infiltrating solid tumours and eliminating cancer cells. The EU-funded CAN-IT-BARRIERS project will obtain new knowledge about systemic and microenvironmental barriers to immunotherapy in the refractory cancers to assess the therapeutic potential of barrier-breaking strategies. The research will focus on how oncogene-expressing keratinocytes elicit an expansion of immunosuppressive myeloid cells in spleen and lymph nodes, and how these cells inhibit the development and activation of CD8 T cells and antigen-presenting dendritic cells.
Objective
The frontier in cancer therapy of orchestrating the immune system to attack tumors is producing unprecedented survival benefit in some patients. The corollary is lack of efficacy both in ostensibly responsive tumor types as well as others that are mostly non-responsive. The basis lies in pre-existing and adaptive resistance mechanisms that circumvent induction of tumor-reactive cytotoxic T cells (CTLs) capable of infiltrating solid tumors and eliminating cancer cells. A priori, cancers induced by expression of human papillomavirus oncogenes should be responsive to immunotherapy: these cancers encode immunogenic neo-antigens – the oncoproteins E6/7 – necessary for their manifestation. Rather, such tumors are poorly responsive to immunotherapies. Results from my lab and others using mouse models of HPV-induced cancer have established an actionable hypothesis: during tumorigenesis, such tumors erect multiple barriers to the induction, infiltration, and killing of cancer cells by tumor antigen-reactive CTLs. These include overarching systemic antigen-nonspecific immunosuppression mediated by expanded populations of myeloid cells in spleen and lymph nodes, complemented by immune response-impairing barriers operative in the tumor microenvironment. A spectrum of models will probe these barriers, genetically and pharmacologically, establishing their functional importance, alone and in concert. A major focus will be on how oncogene-expressing keratinocytes elicit a marked expansion of immunosuppressive myeloid cells in spleen and lymph nodes, and how these myeloid cells in turn inhibit development and activation of CD8 T cells and antigen-presenting dendritic cells. Then we’ll assess the therapeutic potential of barrier-breaking strategies combined with immuno-stimulatory modalities. This project will deliver new knowledge about multi-faceted barriers to immunotherapy in these refractory cancers, helping lay the groundwork for efficacious immunotherapy.
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.
- medical and health sciences basic medicine immunology immunotherapy
- medical and health sciences clinical medicine oncology cervical cancer
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Keywords
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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
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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.
ERC-ADG - Advanced Grant
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Call for proposal
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(opens in new window) ERC-2018-ADG
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1015 Lausanne
Switzerland
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