CPG-ODN FORMULATED WITH COA-ASC16 REDUCES THE DEVELOPMENT OF LUNG METASTASIS: CONDITIONING OF THE PRE-METASTATIC NICHE

BOFELLI LUCIA; CONSTANZA MARIN; DUTTO, JEREMÍAS; FEDERICO N. RUIZ MORENO; BELKYS A. MALETTO; MACCIONI M

Congreso; Reunión anual de sociedades de biociencias SAIC, SAI, FAIC, SAFIS 2022; 2022

CpG-ODN is being widely tested as a prophylactic approach against metastasis. Here we formulated CpG-ODN with a liquid crystal nanostructure of 6-Oascorbyl palmitate (COA-ASC16) to overcome CpG known limitations (short half-life, unfavorable biodistribution).COA-ASC16 has been reported to be a potent adjuvant favoring the CD8+ CTL response in other scenarios. To generate lung metastases, B16.F10 cells (5E4 cells) were injected i.v into C57BL/6mice. The day before and the day after tumor cell inoculation, mice were treated s.c with CpG-ODN or CpG-ODN formulated with CoaASC16 (CpG-ODN/COA). We found that mice treated with cpGODN/COA exhibited reduced incidence of metastasis, lower number of metastatic nodules (p<0,05) and better survival compared to mice treated with CpG-ODN. To investigate if these treatments conditioned the lung as a metastatic niche, mice were immunized twice, every other day, with CpG-ODN or CpG-ODN/COA. 24h later, the lung immune cells were analyzed by flow cytometry. No significant differences were observed in the number of CD45+, CD3+ (neither CD4+ nor CD8+ T cells) and CD19+ cells present in the lungs of both experimental groups. The frequency of NK1.1+ cells was increased in mice treated with CpG-ODN/COA when compared with mice treated with CpG-ODN (p<0,05), particularly NK1.1+CD11B+ cells (p<0,05). Among this population, we found an increase in the frequency of NK1.1+CD11B+LY6C+ cells, which are considered to be a reservoir of potential NK cells upon reactivation, in mice treated with CpG-ODN/COA when compared with mice treated with CpGODN (p<0,001). Besides, mice treated with CpG-ODN/COA showed a reduced frequency of monocytes (Ly6C+CD11B+ cells) when compared with CpG-ODN treated mice (p<0,05). Thus, CPG-ODN/COA reduces the development of lung metastasis, reshaping theimmune compartment present in the lung. Further studies should be done to decipher the immune mechanisms underlying the lung conditioning of CpG-ODN and CpG-ODN/COA.