Research of new immunotherapy for colorectal liver metastasis using T-cell negative pathway

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10579
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nara Medical University
• Principal Investigator: Hokuto Daisuke 奈良県立医科大学, 医学部, 助教 (70526821)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 大腸癌肝転移 / 免疫療法 / Ｔ細胞不活化経路

Outline of Final Research Achievements

The aim of this study was to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM). We examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. High HVEM expression was observed in 49 patients (47.1%) with CRLM. HVEM expression was not associated with age, gender, the administration of preoperative chemotherapy, tumor size, the number of tumors, or histological differentiation. The high HVEM group exhibited significantly worse overall survival (OS) than the low HVEM group (P=0.002). Multivariate analysis revealed that high HVEM expression in CRLM is an independent poor prognostic factor for OS (HR: 3.35, 95%CI: 1.41-7.93, P=0.006). The numbers of tumor-infiltrating CD8+ and CD45RO+ T cells were significantly lower in the high HVEM group than in the low HVEM group.
Conclusions. Tumor HVEM expression might play a critical role in CRLM.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

大腸癌肝転移は大腸癌の予後に最も影響を与える転移であり，その制御は重要である．肝切除により治癒する場合もあるが，切除不能の場合は化学療法がおこなわれる．しかし，化学療法の効果は限定的であり，さらなる治療の開発が求められている，
本研究により，大腸癌肝転移に対してHVEMをターゲットとした免疫療法の効果が期待されうることが判明した．この結果はこれまでに報告されておらず，非常に意義のある研究と思われた．