MicroRNAs involvement in dendritic cell immune functions in the context of immunogenic cancer cell death

LAMBERTI MJ; MONTICO B; RAVO M; GIURATO G; NIGRO A; STEFFAN A; WEISZ A; STELLATO C; CASOLARO V; DAL COL J

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI); 2023

The interaction between tumor cells and immune cells is a critical aspect of cancer progression, and microRNAs (miRNAs) have been identified as important players in this crosstalk. The present study aims to investigate the role of miRNAs in dendritic cell (DC) immune functions in the context of immunogenic cancer cell death (ICD), which is a type of cell death induced by certain cancer therapies that activates the host immune system. Here, we applied a pre-established model of ICD induced in tumor cell lines by the combination of retinoic acid (RA) and interferon-α (IFNα). Immunogenic tumor cell lysates (iTCLs) obtained from cells treated with RA/IFNα were used as a tumor antigen/adjuvant source for DC loading. Next-generation sequencing was employed to identify differentially expressed miRNAs in iTCLs and iTCLs-pulsed DCs, and validation assays were conducted to confirm the presence of specific miRNAs in recipient DCs. We found that two miRNAs, miR-4284 and miR-212-3p, previously described upregulated in tumor cells during ICD, were present in iTCLs and could be displayed in their immature and/or mature forms in iTCLs-pulsed DCs. The integration of miRNA-mRNA functional networks revealed potential targets involved in cell surface receptor signaling pathways, particularly the IL-1 pathway. The secretion of cytokines linked to the IL-1 signaling family was further confirmed using a bead-based multiplex assay. These findings suggest that intercellular communication involving miRNA during ICD could modulate immune mechanisms, with an impact on DCs functions. This study suggests that miRNAs, among other damage associated molecular patterns, play a role in modulation of DC immune functions in the context of ICD in particular by targeting genes related to cell surface receptor signaling pathways, particularly the IL-1 pathway. However, the molecular mechanisms underlying miRNA transfer from dying tumor cells to DCs remain to be elucidated.