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Targeting innate lymphoid cells (ILCs) to reinvigorate anti-tumor immunity

As innate cells and a rapid source of distinct cytokines, Innate Lymphoid Cells (ILCs) have emerged as key orchestrators of immunity, inflammation and homeostasis. We are interested in examining the roles of ILCs in human anti-tumor immunity. By combining single cell transcriptomic and epigenetic profiling with multiparametric flow cytometry, we are able to assess quantitative and qualitative alterations of ILCs directly in cancer patients. Using ex-vivo ILCs and short-term in vitro expanded ILC lines, allows us to dissect the cross-talk between ILCs and adaptive immune cells, myeloid, endothelial and cancer cells. By interfering in vitro and in vivo with identified targetable pathways, we can explore therapeutic options that exploit ILC biology, in particular (i) aiming to optimize adjuvants that target ILC subsets, favouring tumor rejection (ii) using ILC lines expanded in vitro as a cell therapy based approach, (iii) using cytokines, small molecular compounds and epigenetic regulators that may promote expansion and/or reprogramming of endogenous ILCs in cancer patients.

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Figure 1. Imaging flow cytometry on human peripheral blood ILCs (by the Amnis Image stream Instrument).

High-throughput analysis of tumor-specific CD4 T cells for cancer immunotherapy

Increasing evidence highlights the crucial roles of tumor-antigen and neo-antigen specific CD4 T cells in anti-tumor immunity. We have adopted and developed cutting-edge technologies for high-throughput analyses at the single cell level, allowing us to focus on the quantitative and qualitative evaluation of natural and therapy-induced tumor-specific CD4 T cell responses. We aim to identify the most potent T cells and best-of-class T cell receptors (TCRs), enabling their rapid and cost-effective isolation and validation in clinical trials, thus paving the way for immediate translational and economic impact. Furthermore, with our work we aim to gain new scientific insight into the determinants of CD4 T cell fitness versus exhaustion, which will contribute to biomarker discovery and immune cell engineering for personalized cancer immunotherapy.

Figure 2. CD4 T cell-mediated cytotoxicity of tumor cells visualized at the single cell level, in real-time, using a novel picowell nanochip (collaboration with Prof H. Altug, EPFL).

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