Effects of adoptive T-cell immunotherapy on immune cell profiles and prognosis of patients with unresectable or recurrent cholangiocarcinoma

Int J Cancer. 2024 Feb 15;154(4):738-747. doi: 10.1002/ijc.34716. Epub 2023 Sep 7.

Abstract

The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αβ T cells alone or combined with chemotherapy. ICP were evaluated by flow cytometry. There were 14 patients with intrahepatic cholangiocarcinoma (iCCA) and four with distal cholangiocarcinoma (dCCA). After one course of treatment, nine iCCA and four dCCA had progressive disease (PD), while five iCCA had stable disease (SD). Median overall survival (OS) was prolonged to 21.9 months. No significant differences were observed in OS between the PD and SD groups of iCCA. The frequency of helper T cells (HT) in iCCA decreased from 70.3% to 65.5% (P = .008), while that of killer T cells (KT) increased from 27.0% to 30.6% (P = .005). dCCA showed no significant changes of immune cells. OS was prolonged in iCCA with increased frequencies of CD3+ T cells (CD3) (P = .039) and αβ T cells (αβ) (P = .039). dCCA showed no immune cells associated with OS. The frequencies of CD3+ T cells and αβ T cells in the PD group for iCCA decreased from 63.5% to 53% (P = .038) and from 61.6% to 52.2% (P = .028), respectively. In the SD group, the frequency of HT decreased from 65.8% to 56.9% (P = .043), whereas that of KT increased from 30.1% to 38.3% (P = .043). In conclusions, ATI affected ICP and prolonged OS. Immune cells involved in treatment effects differed according to the site of cholangiocarcinoma.

Keywords: adoptive T-cell immunotherapy; cholangiocarcinoma; flow cytometry; immune cell profiles; αβ T cells.

MeSH terms

  • Bile Duct Neoplasms* / pathology
  • Bile Duct Neoplasms* / therapy
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma* / therapy
  • Humans
  • Immunotherapy
  • Prognosis