Abstract 1327: Variable impact of chemotherapy +/- cetuximab on immune modulation in a prospective cohort of 163 cancer patients
Authors: Lo Nigro Cristiana , Monteverde Martino , Etienne-Grimaldi Marie-Christine , Strola Giuliana , Lattanzio Laura , Vivenza Daniela , Tonissi Federica , Ghiglia Annalisa , Merlano Marco , Milano Gerard 
Published: August 2015

Abstract
Introduction: Immunomodulation by anticancer agents is currently of major interest. We prospectively examined in 163 advanced cancer patients the impact of chemotherapy, combined or not with cetuximab, on relevant immune cell profile. Patients and Methods: 72 metastatic colorectal cancer patients received FOLFIRI, associated (N = 60) or not (N = 12) with cetuximab (Cetux), and 91 head&neck squamous cell carcinoma patients received 5FU+platinum-based chemotherapy, associated (N = 69) or not (N = 22) with Cetux. Median follow-up was 12.9 months (96 deaths). Phenotyping (Beckman coulter flow cytometer) of peripheral-blood lymphocytes was performed at baseline and after 2-month treatment. T cells were defined as CD3+ (irrespective of CD56), NK cells as CD3- CD56+, NKT cells as CD3+ CD56+, and invariant CD1d-restricted natural killer T (invNKT) cells were characterized by coexpression of T-cell antigen receptor-Vα24 and -Vβ11 along with CD3+ and CD56+. Results: Analysis of cell count evolution at 2-month showed that 5FU+platinum negatively significantly modulated both T, NK, NKT and invNKT cells, with a median decrease of 45% to 69% relative to baseline, whereas FOLFIRI had no significant impact. In combination with Cetux, the decrease observed with 5FU+platinum was significantly attenuated for T cells, and a similar trend was observed in NKT cells (Table). In contrast, the combination of Cetux with FOLFIRI induced a significant decrease in NK cells. Overall survival was not related to the evolution of any immune cell type, either in Chemo or Chemo-Cetux groups. Conclusion: Present results on the differential modulation of peripheral immune cells by cetuximab-chemotherapy draw attention and may be of importance in the context of future combinations with immunotherapy.
Intra-patient cell count change (%) at 2 months relative to baseline:
5FU-Platinum group5FU-Platinum + Cetux groupInter-group stat**MedianStat*% of patients with decreaseMedianStat*% of patients with decreaseT cells-66p&lt;.00196%-36p&lt;.00176%p = .002NK-69p = .00287%-56p&lt;.00189%nsNKT-51p = .02082%-28ns61%p = .089invNKT-45p = .00478%-38p&lt;.00172%nsFOLFIRI groupFOLFIRI + Cetux groupInter-group stat**MedianStat*% of patients with decreaseMedianStat*% of patients with decreaseT cells-15ns73%-3ns56%nsNK-22ns55%-43p&lt;.00180%p = .031NKT+10ns27%-1ns51%nsinvNKT-32ns55%-16p = .00855%nsp value of Wilcoxon paired-test* or Mann-Whitney test**. ns means not significant.
Citation Format: Cristiana Lo Nigro, Martino Monteverde, Marie-Christine Etienne-Grimaldi, Giuliana Strola, Laura Lattanzio, Daniela Vivenza, Federica Tonissi, Annalisa Ghiglia, Marco Merlano, Gerard Milano. Variable impact of chemotherapy +/- cetuximab on immune modulation in a prospective cohort of 163 cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1327. doi:10.1158/1538-7445.AM2015-1327