Role of intratumoral infiltrating macrophages after transarterial immunoembolization for hepatocellular carcinoma

J Hepatobiliary Pancreat Sci. 2016 May;23(5):298-304. doi: 10.1002/jhbp.342. Epub 2016 Apr 4.

Abstract

Background: Preoperative transarterial immunoembolization (TIE) for hepatocellular carcinoma (HCC) is effective for preventing recurrence. We aimed to investigate the intratumoral and peritumoral M1 macrophage-induced immune response following TIE treatment.

Methods: We compared 13 patients treated with TIE between 2003 and 2009 (TIE group) and 13 patients treated with surgery alone during the same period of time at our institute (control group) using an immunohistological study with CD68 and CD163 antibodies.

Results: No significant differences in clinicopathological characteristics, except for surgical time, were observed between the two groups. The 3-year recurrence-free survival outcome of the TIE group was quite different from that of the control group (100% vs. 38.5%, P = 0.034). In the histological investigation, lytic necrosis and coagulation necrosis of the main tumor along with the presence of multinuclear giant cells were observed in 10 of the 13 patients in the TIE group. The immunohistological study showed that not only the numbers of intratumoral CD68(+) cells, but also the numbers of intratumoral and peritumoral CD8(+) cells were significantly increased in the TIE group.

Conclusions: The suppression of tumor recurrence induced by preoperative TIE might be induced by intratumoral M1 macrophages that are activated by OK-432 and fibrinogen.

Keywords: Hepatocellular carcinoma; Immune response; Macrophage; OK-432.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Catheterization, Peripheral / methods*
  • Chemoembolization, Therapeutic / methods*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intra-Arterial
  • Liver / pathology*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Picibanil / administration & dosage*
  • Receptors, Cell Surface / immunology
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD163 antigen
  • CD68 antigen, human
  • Receptors, Cell Surface
  • Picibanil