CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

概要

〔目　 的(Purpose)〕
　Triple-negative breast cancers (TNBCs) represent high-grade tumors that are large and commonly associated with regional node metastases, and recur at distant sites, especially within the first 5 years of diagnosis. Because of lacking the ER, PR, HER-2 receptors, TNBCs are insensitive to anti-hormone therapy or Herceptin. Therefore our research aim is that to finding a new gene therapy for TNBCs.

〔方法ならびに成績(Methods/Results)〕
　we combined CXCL2 (CXC chemokine ligand 2) plasmid DNA with inactivated Sendai virus (hemagglutinating virus of Japan)-envelope (HVJ-E) to treat with 4T1 orthotopic and lung metastatic models. We also went through a variety of experiments to find out the mechanism of the tumor suppression by the combination of CXCL2 DNA and HVJ-E (C/H) treatment.
　Here, we found the combination of CXCL2 DNA and HVJ-E (C/H) suppressed the growth of murine breast cancers in orthotopic syngeneic models by enhancing cytotoxic T lymphocytes and inhibited lung metastasis of breast cancer from primary lesions. N1 type neutrophils (CD11b+ Ly6G+ FAS+) increased in the tumor microenvironment with C/H treatment, and tumor suppression and cytotoxic T lymphocyte activation from C/H was blocked after administrating anti-neutrophil antibodies, which indicates the role of N1 type neutrophils in cancer immunotherapy. We also demonstrated that the anti-tumor activities of C/H treatment were enhanced by the administration of anti-PD-1 antibodies through neutrophil-mediated cytotoxic T lymphocyte activation.

〔総　 括(Conclusion)〕
　C/H treatment enhanced the tumor suppression effect of anti-PD-1 antibody treatment in a breast cancer model. Our findings indicated that the triple combination of C/H and anti- PD-1 antibodies may be an improvement in cancer immunotherapy.