Impact of combining TNF blockade and immune checkpoint inhibitors on liver metastases and immune responses.

Postdoctoral position

Application deadline: 30 Nov 2023

Institute: Cancer Research Center of Toulouse
Country: France
More information: https://www.crct-inserm.fr/en/melasphinx_en/

While most studies in immuno-oncology focus on primary tumors, the majority of patients treated with immunotherapies suffer from disseminated metastatic disease and, in many cases, liver metastases. Liver metastases are common, confer a poor prognosis, constitute a clear unmet medical need, and are strongly associated with resistance to immunotherapy. Our group recently showed the potential benefit of combining TNF blockade and immune checkpoint inhibitors in mouse models of cancer, including melanoma (Nat. Commun. 2017) and applied these results to the clinic in patients with advanced melanoma (Clin. Cancer Res. 2021). We hypothesize, based on preliminary data, that TNF, along with other immunosuppressive cytokines, is essential in promoting tumor escape from the immune system to liver metastases, with potential redundancies when considering them as therapeutic targets. As part of a European project (TRANSCAN), we aim to evaluate (i) the putative links between TNF and other immunosuppressive cytokines in liver metastases not only in mice but also in patients enrolled in early clinical trials; (ii) the impact of TNF blockade on liver metastases in mice as well as on patient-derived organotypic slice cultures. Our studies will focus on patient-derived samples as well as syngeneic animal models of liver metastases. Importantly, biopsies of liver lesions taken before and during treatment in early phase clinical trials testing inhibitory compounds will be studied. Our project will evaluate TNF and other immunosuppressive cytokines as isolated therapeutic targets or in potential synergistic treatment combinations, identify predictive biomarkers of response to cytokine blockade, and uncover novel therapeutic targets for the treatment of liver metastases. The candidate will work in a center specializing in cancer research located on the Toulouse oncopole. This center has a highly developed technical platforms for imaging, cytometry, transcriptomics and animal facilities. It is closely linked to the hospital dedicated to cancer care. The recruited person will join a team working on immuno-oncology for ten years and specialized in melanoma, TNF signaling and lipid metabolism. This project will also be part of a very enriching international collaboration aimed at developing new therapeutic approaches for the treatment of cancer.

Candidate profile: immunologist with expertise in experimental models of cancer and immunotherapy in mice.
How to apply? Candidacy, including motivation letter and CV, should be sent to Prof. Bruno Ségui by email (bruno.segui@inserm.fr) before November 30, 2023.
Position available: from November 1, 2023.
Funding: 2-year contract financed by INCa as part of a European TRANSCAN project (iParaCyts).

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