IL4 induced gene 1 and tumor escape in melanoma: An emerging biomarker for prognosis and resistance to immunotherapy

Enzymes catabolizing essential or semi-essential amino acid play a crucial role in immunosuppression at the tumor site. Among those, IL4-induced gene 1 (IL4I1), a phenylalanine oxidase expressed in the TME of most solid cancer types, inhibits T lymphocytes. We have evidenced its role in tumor escape in experimental murine models of mela noma. We have also detected IL4I1 expression in situ in most of human primary cutaneous melanoma that may be relevant to predict prognosis. Interestingly, the proportion of IL4I1+ cells correlates negatively with the presence of cytotoxic CD8+ T cells and positively with the presence of regulatory T cells. Collectively, our findings strengthen the rationale for therapeutic targeting of IL4I1 as a key immune regulator.
The project aims at elucidating the IL4I1-dependent-protumoral mechanisms using melanoma samples from patients treated or not with anti-PD1 and various mouse models we set-up and. This project relies on multiple up-to-date technical approaches such as in situ tissue analysis, laser microdissection and scRNA-seq analyses, combined with in vivo monitoring of melanoma development after IL4I1 targeting.
We invite applications from highly motivated junior candidates (i.e. <2 years of post-doctoral experience). The candidate should have a strong background in Immunology & cancer biology. Prior experience in imaging and cytometry is required. Excellent time management, organisational abilities and proficient communication skills are essential.

Type: CDD Funding INCa

Organization: INSERM
Beginning: expected in October 2021 Length of contract: 10 months (possibility of extension)

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