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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Quantifying systemic immunosuppression to personalize cancer therapy

Alternative title: Kvantitativ analyse av immunsuppresjon for utvikling av persontilpasset kreftbehandling

Awarded: NOK 2.9 mill.

The immune system is now considered to contribute to the effect of most cancer therapies. Some immune cells appear to be beneficial, while other immune cells may mediate resistance to therapy and promote cancer growth. The focus of this project, is to study the role of an immune cell type considered to be detrimental, the so-called myeloid derived immunosuppressive cells (MDSC). Particularly, the frequency of MDSC in blood has been associated to poor prognosis and resistance to treatment in several cancers. Nonetheless, no effort to translate this key concept into clinical practice for stratifying cancer patients and possibly increasing their curability by personalizing treatment strategy, has been performed so far. The Serpentine Project is committed to achieve this goal in a concerted fashion by exploiting the clinical and scientific expertise of the Consortium members, to provide a new, strong, affordable and easy prognostic/predictive biomarker. We will measure the frequency of MDCS in blood in cancer patients, and relate this to their clinical outcome. A Myeloid Index Score (MIS), recently developed within the Consortium, will be assessed and recorded in a shared in-cloud database together with clinical data and additional information. In parallel, MDSC and plasma will be studied in depth by several methods, to improve our understanding of MDSC subsets, and potentially identify novel biomarkers MDSC-targeting strategies that may be used for cancer therapy.

Most cancer therapies are reported to rely on the contribution of host immunity for exerting clinical benefit. Efficacy is usually accompanied by the increase of T cell tumor infiltrate, while resistance is featured by the accrual of myeloid immunosuppressive cells (MDSC). Particularly, the frequency of MDSC in blood has been associated by many groups, including ours, to poor prognosis and resistance to treatment in several malignancies. Nonetheless, no effort to translate this key concept into clinical practice for stratifying cancer patients and possibly increasing their curability by personalizing treatment strategy, has been performed so far. The Serpentine Project is committed to achieve this goal in a concerted fashion by exploiting the clinical and scientific expertise of the Consortium members, to provide a new, strong, affordable and easy prognostic/predictive biomarker based on quantifying systemic immunosuppression. A prospective multicentric study enrolling patients with representative neoplasms treated with standard therapy, will be performed and blood samples collected at baseline and during treatment for MDSC-related analyses. A Myeloid Index Score (MIS), obtained by 4-color cytometry recently developed within the Consortium, will be assessed and recorded in a shared in-cloud database together with clinical data and additional information collected throughout the study. Baseline MIS will be correlated with PFS and OS, to define a risk of therapeutic resistance. In parallel, blood MDSC and plasma will be studied in depth by genomic, phenotypic and transcriptional profiling to explore MDSC subsets and identify novel biomarkers and MDSC-targeting strategies. The Serpentine is designed to provide the first tool for assessing systemic myeloid-mediated immune suppression in cancer patients and discovering new drug modulating strategies, to help tailoring treatments and improving cancer curability in a real life setting.

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering