Cancer evasion from the immune surveillance is a recent but major hallmark of cancer. Engagement of the immune checkpoints induce the inactivation of T lymphocytes. The overexpression of these ligands by tumor cells and immunosuppressive cells leads to immune escape. The targeting of inhibitor immune checkpoints constitutes a new and promising therapeutic option against chronic lymphocytic leukemia (CLL). Until today, PD-1 and PD-L1 are the prime targets. The anti-PD-L1 antibody therapy decreases inflammation in CLL and proved its therapeutic efficacy by reducing the tumor burden in the murine Eμ-TCL1 CLL mice. However, many other immune checkpoints are crucial regulators of anti-tumor recognition.

This project is studying the efficacy of inhibiting other immune checkpoints in the Eμ-TCL1 mouse model of CLL. Expressed par NK and Treg cells, these markers are negative immune regulators and are also present on the surface of exhausted T cells in CLL. This project also aims at characterizing the immune microenvironment in this mouse model with or without treatment. For this purpose, we analyze the expression of multiple surface and intracellular markers by mass cytometry, an innovating technique combining the advantages of flow cytometry and mass spectrometry. This project will allow us to identify new cellular populations which could be used as biomarkers for the response to treatment and potential new therapeutic targets.

Funding

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Project financed by:undefined

Télévie IPCI LLC 7.4508.16

Télévie IPCI LLC-2 7.6504.18

Télévie Treg LLC 7.4501.18

Télévie HAB-LLC 7.4502.19

Télévie TIME-LLC 7.4529.19

 

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Dr. Martina Seiffert undefined

Dr. Sascha Dietrich undefined

Pr. Eric Solary  undefined

Dr. Ingo Ringshausenundefined

Dr. Georges Lacaud  undefined

Wierz et al, Blood 2018

Wierz et al, OncoImmunology 2018

Largeot, Pagano et al., Cells 2019

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