Immunomonitoring

One of the main issues in the evaluation of immunotherapy efficiency is to reproduce the tumor microenvironment complexity. Conventional 2D tumor cell line culture certainly does not allow to recapitulate the heterogeneity of human tumor landscape nor its surface marker expression pattern or tumor metabolism.

The use of 3D cell culture allows to mimic the structure of tumors and their complexity ex vivo. In depth phenotyping of human tumors allows us to define the diversity of tumor microenvironments. To model these microenvironments using human 3D cell culture, we culture patient’s immune cells with their own tumor organoid or explant to allow the recapitulation of immune microenvironment.

We recently acquired a microfluidics 3D culture system to study the interactions of tumors with autologous circulating cells in response to immunotherapy in human preclinical settings

IDA53 is a phase II clinical trial evaluating the safety and the efficacy of ibrutinib in combination with daratumumab in relapsed or refractory high-risk chronic lymphocytic leukemia (CLL) with p53 dysfunction (NCT03734198). Ibrutinib, a Burton's tyrosine kinase inhibitor, and daratumumab, a monoclonal antibody directed against CD38, can potentially induce synergistic or antagonistic immunomodulatory effects on anti-tumor immunity.

In this context, the present ancillary study aims to compare the impact of this combination on the immune contingent in patients with optimal clinical response, or resistant to this treatment. Deep phenotyping of patients’ samples will be performed by spectral cytometry.

This study will make it possible to explore the mechanisms of resistance to the ibrutinib/daratumumab combination in CLL, with the ultimate aim of establishing a rationale to guide ibrutinib/monoclonal antibody combinations in future clinical trials.

Pancreatic adenocarcinoma (PDAC) is a major public health problem. Its prognosis is poor, with a 5-year survival rate estimated at 11% in France. Surgery is the only curative treatment to date, but 80% of patients are diagnosed at an advanced stage, which precludes surgical treatment. Despite considerable efforts over the last few years to develop new management strategies, the results in terms of improved survival and therapeutic innovation remain very disappointing to date. Early detection of PDAC is therefore a major challenge that could improve prognosis by making it accessible to surgery.

The early carcinogenesis of PDAC is characterised by a profound remodeling of the immune landscape, and some immune alterations precede the early steps of tumorigenesis. These changes can be detected in the peripheral blood of patients. We therefore hypothesize that detection of these changes can provide a reliable surrogate for immune remodeling in precancerous lesions and will allow accurate identification of patients with early malignant transformation to help us better guide the optimal timing of surgical treatment.

Prostate cancer is one of the most common cancers in men worldwide, and remains an incurable disease when diagnosed at the metastatic stage. The aim of this project is to identify new prognostic immune biomarkers from the plasma of patients with hormone sensitive metastatic prostate cancer.

We characterize the soluble forms of our proteins of interest, in particular the form associated with extracellular vesicles, using phenotyping by spectral cytometry. We aim to define their impact on immune cells, in vitro and ex vivo, with PBMCs deep phenotyping by multiparametric spectral cytometry. Analyses of these data using artificial intelligence tools will enable the identification of immune alterations associated with prostate cancer, and help in the development of new immunotherapy strategies for this pathology.