Abstract 2574: Interleukin-7 (CYT107) treatment in lymphopenic 1st line metastatic breast carcinoma patients treated with chemotherapy regimen (Capecitabine) favors the restoration of T-cell subsets number
Authors: Menetrier-Caux Christine , Ray-Coquard Isabelle , Cropet Claire , Verronese Estelle , Bachelot Thomas , Tredan Olivier , Garin Gwenaelle , Heudel Pierre , N'Kodia Axelle , Delgado Ana , Bardin-Dit-Courageot Christine , Rigal Chantal , Clapisson Gilles , Chabaud Sylvie , Perol David , Rebattu Paul , Croughs Thérèse , Pasqual Nicolas , Manuel Manuarii , Morre Michel , Blay Jean-Yves , Caux Christophe 
Published: May 2015

Abstract
Introduction: We previously showed that T (&lt;1000/µl) or CD4 (&lt;450/µl) T cell lymphopenia detected before chemotherapy initiation predicts early death for metastatic breast cancer (MBC) patients. ELYPSE-7, a placebo-controlled clinical trial aimed to evaluate impact of CYT107 treatment (before or during chemotherapy) on CD4 T cell count (see Ray-Coquard abstract). Our ancillary study reports in-depth quantitative and functional changes in circulating immune populations.
Methods: Lymphocytes, NK, monocytes and DC subpopulations quantification and functional competence after reactivation (PMA/ionomycin, TLR7/8-Ligand) were assessed by multiparametric flow-cytometry (surface markers/ intracytoplasmic cytokines) on fresh whole blood (D0, D21, D57, D78, EOS). Impact of CYT107 treatment before (D0-D21) or during (D57-D78) chemotherapy on immune parameters was assessed.
Results: At inclusion, 20 patients presented strong quantitative alteration of all lymphocytes subsets compared to a healthy donor women cohort (n=30). Inflammatory monocytes (infl-Mo) and DC subsets were quantitatively reduced. CD4 CD45R0+ T (IFNγ/IL-2), Tγδ cells and NK (IFNγ) cytokine productions were altered independently of quantitative alterations highlighting the importance to assess both. Pre-chemotherapy, CYT107 significantly increased CD3 T cell absolute number (median relative evolution: CYT107+128.5%[39;606cells/µL] vs placebo +1.6%[-34;85cells/µL], p=0.002) involving both CD4 (p=0.002) or CD8 (p=0.006) T cells and naïve (CD4:p=0.005 and CD8:p&lt;10-3) and memory subsets (CD4:p&lt;10-3 and CD8:p=0.008). CYT107 pre-chemotherapy induced a Treg number increase (p=0.017) remaining however in the normal range. In contrast, B cells, infl-Mo, DC and NK absolute numbers were not significantly modified. During chemotherapy (D57-D78, n=11), T cell absolute number increases in CYT107 group vs placebo (median relative evolution: CYT107 +61.5%[-11.1;229.7cells/µL] vs placebo -0.5%[-30.7;73.5cells/µL], p=0.083), CD4 and CD8 subsets being affected and in particular CD8 naive(median relative evolution: CYT107 +75.8%[39.0;314.6cells/µL] vs placebo -0.6%[-18.7;48.4cells/µL], p=0.022) and memory subsets (median relative evolution: CYT107 +72.1%[-21.9;282.7cells/µL] vs placebo -8.6%[-43.3;32.8cells/µL], p=0.055). Of importance, no significant modulation of immune cells functional competence was observed upon CYT107 treatment.
Conclusion: CYT107 administered before chemotherapy, increases all T cell subsets absolute number but no other compartments without affecting their functional responses. Interestingly, during chemotherapy, CYT107 induces an increase of CD8 memory cells, known to play a role in long lasting defense against tumors.
Citation Format: Christine Menetrier-Caux, Isabelle Ray-Coquard, Claire Cropet, Estelle Verronese, Thomas Bachelot, Olivier Tredan, Gwenaelle Garin, Pierre Heudel, Axelle N'Kodia, Ana Delgado, Christine Bardin-Dit-Courageot, Chantal Rigal, Gilles Clapisson, Sylvie Chabaud, David Perol, Paul Rebattu, Thérèse Croughs, Nicolas Pasqual, Manuarii Manuel, Michel Morre, Jean-Yves Blay, Christophe Caux. Interleukin-7 (CYT107) treatment in lymphopenic 1st line metastatic breast carcinoma patients treated with chemotherapy regimen (Capecitabine) favors the restoration of T-cell subsets number. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2574. doi:10.1158/1538-7445.AM2014-2574