72P - The immune modulation role of low dosage of cyclosporin-A (ldCSA) in the antitumor response of CD8+ T lymphocytes (CD8+Tcells) and the implication...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Personalised Medicine
Presenter CAMILA Flores
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors C. Flores1, O. Hermine2, T. Maciel2, R. Rignault2, J. Rossignol2, Y. Lepelletier2
  • 1Inserm U1163, Institut Imagine, 75015 - Paris/FR
  • 2Inserm U1163, Institut IMAGINE, 75015 - Paris/FR



The involvement of Nrp1 in the formation of the immunological synapse was first described by our research team, when demonstrating an increased expression of Nrp1 on the surface of activated CD8+Tcells and dendritic cells. Presently, we thus investigated the role of ldCSA in the modulation of CD8+T cells activation and its antitumor effect along to the negative regulation of Nrp1 expression while preserving the T cells activation.


In vivo, C57BL6 mice were challenged with B16F10GFP murine melanoma for tumor monitoring and phenotypic analysis. Cohort’s treatments comprised: ldCSA (CSA serum 25ng/ml), high dosage of CSA (CSA serum 100ng/ml) and control group (vehicle only). Phenotypic analysis was assessed by flow cytometry for tumor-infiltrating cells, activation markers, exhaustion marker (PD1) and Nrp1 expression on CD8+Tcells. NSG mice were challenged with B16F10GFP for tumor growth monitoring. In vitro, mice and human CD8+T cells sorted received no, low or high dose of CsA for 48h and assessed by flow cytometry towards activation markers, PD1 and Nrp1.


For C57BL6 mice, the cohort treated with ldCSA had a slowed tumor growth (p = 0.05). For NSG mice devoid of T Cells, there was no effect of ldCSA suggesting that the effect observed depends on immune cells instead of a direct effect of CSA on tumor cell growth. C57BL6 experiment showed a lower infiltration of CD8+Tcells in tumor bed, while these cells were more activated when compared to the no dose or high dose treated cohorts. For the ldCSA cohort, CD8+Tcells infiltrating the tumor exhibited a reduction of PD1/Nrp1 expression. For in vitro experiments, upon treatment with ldCSA, it was observed a decreased expression of PD1 and NRP1 on sorted human and mice activated CD8+T cells (p = 0.01) and the upkeep IFNγ production.


Our results support an innovative effect of ldCSA, demonstrating an efficacy in amplifying the immune response of CD8+Tcells. It suggests an effect linked to negative regulation of Nrp1 and PD1. Experiments using NRP-1KO CD8+T cells are ongoing to confirm the CSA mechanism of action. The identification of ldCSA as new long-term therapeutic antitumor strategy deserves further larger studies.

Clinical trial identification

Legal entity responsible for the study

Institut Imagine




All authors have declared no conflicts of interest.