Tim3 is a biomarker and a therapeutic tools in primary resistance to Nivolumab in lung cancer patients Emeric Limagne1,2, Corentin Richard1,2, Marion Thibaudin1,2, Jean David Fumet1,2, Francois Ghiringhelli1,2 1CentreGeorges-François Leclerc, Dijon, France; 2Cancer Biology Transfer Platform, Dijon, France Hypothesis: Nivolumab (anti PD-1) are approved for non-small cell lung cancer after failure of first line chemotherapy. However, only a quarter of patient benefits from this therapy, in this context robust predictive biomarker is an unmet need and we hypothesized that immune blood parameters can predict outcome.
Methods: We studied a cohort of metastatic lung cancer (n=61) treated in second or third line by Nivolumab and 12 sex and age matched healthy volunteers as a control. We performed analyses of various myeloid and lymphoid markers using flow cytometry (257 variables) before treatment, after 15 and 30 days of therapy.
Results: By searching early biomarker of resistance we observed that accumulation of Tim3 expressing T cells and accumulation of MDSC are predictive or resistance. T cells and MDSC expressing Tim3 at baseline also predict resistance to Nivolumab. Combination of anti-PD1 and anti-Tim3 reverses in vitro primary resistance of lung cancer patients PBMC to anti-PD1. Similarly this combo therapy reverses primary resistance to anti-PD1 in lung mice models.
Conclusions: Taken together our data underline that Tim3 could be used as biomarker of primary resistance to anti PD1 and also as a therapeutic tool to reverse this resistance.
Credits: None available.
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