Nasopharyngeal carcinoma (NPC) is endemic in Southern China. The main characteristic of a cancer cell is its resistance to undergo apoptosis; therefore, reversing this resistance may represent the best approach for the treatment of cancer. Additionally, NPC is well-known to be heavily infiltrated by lymphocytes and constitute a unique but poorly defined tumor microenvironment (TME). We aimed at delineating and defining the contribution of idronoxil (IDX) in restoring sensitivity to apoptosis and potentially modulating the immune microenvironment of NPC.
The antitumor and immunomodulatory activities of chemotherapeutic drug cisplatin (Cis) and/or IDX were tested in authentic EBV-positive NPC-derived cell lines (C666, C17 and NPC43). The IC50 were evaluated and the migration and proliferation of cells treated with IDX and/or Cis were investigated by Transwell and XTT, respectively. Immune cell phenotypes and migratory analyses were measured by flow cytometry on Cis/IDX-pretreated NPC cell lines cocultured with HLA-matched PBMC.
IDX and Cis inhibited NPC migration, cell proliferation and apoptosis (IC50 for IDX was 2µM; IC50 for Cis was 0.6µM). Low-dose of IDX (1-2 μM) not only sensitizes cancer cells to Cis via apoptosis, but also promotes peripheral blood mononuclear cells (PBMCs) migration towards tumor (2.4-fold, p=0.0052). Among various immune lineages, IDX, but not Cis, significantly promoted the migration of CD8, but not CD4 T cells in the cocultures.
IDX was shown to induce apoptosis in NPC cells while inhibiting their migration. Moreover, the ability of IDX to modulate T cell populations indicates the drug’s potential to enhance the efficacy of current chemotherapy treatments in NPC by upregulating cellular trafficking to the cancer cell.