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<p>Immune checkpoint inhibitor (ICI) based combined neoadjuvant/conversion therapy (NAT) is increasingly utilized in the management of initially unresectable intrahepatic cholangiocarcinoma (iCCA). However, immune-related pathologic response (irPR) features and immunotherapeutic response score (ITRS) remain poorly understood in iCCA.</p><p>This study enrolled 147 iCCA patients who received NAT. irPR features (tumor infiltrating lymphocyte, tertiary lymphoid structure, lymphoid aggregate, plasma cell infiltration, granuloma, neutrophil, foamy macrophage, cholesterol cleft, hemosiderin macrophage, giant cell, neovascularization and mature fibrosis) were accessed on routinely processed hematoxylin-eosin stained post-NAT surgical resection specimen tumor bed slides. Kaplan-Meier and Cox regression analyses were used to investigate irPR features and ITRS correlations with recurrence-free survival (RFS) and overall survival (OS).</p><p>The irPR features were identified in the post-NAT surgical resection specimen of iCCA. Six irPR features were included in ITRS. A binary ITRS scheme was developed, wherein patients classified as ITRS-low exhibited significantly better OS (hazard ratio [HR]:3.03; 95% confidence interval [CI]: 1.55–5.89, <i>P</i> &lt; 0.01) and RFS (HR:1.94; CI: 1.24–3.03, <i>P</i> = 0.03) compared to those in the ITRS-high group, based on univariate analysis. In multivariate analysis including lymphovascular invasion, perineural invasion and major pathologic response, ITRS scheme was also found to be an independent prognostic factor for OS (HR: 1.95; 95% CI: 1.02–4.27, <i>P</i> = 0.04).</p><p>An irPR features-based ITRS scheme significantly predicts OS and RFS in post NA iCCA patients. The ITRS is feasible for implementation in routine diagnostic pathology practice and offers novel insights into resistance mechanisms associated with immunotherapy.</p>

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Immune-related pathologic response (irPR) features and immunotherapeutic response score (ITRS) predict survival following neoadjuvant/conversion combined immunotherapy in intrahepatic cholangiocarcinoma

  • 期刊论文

  • 发表日期：

    2026年7月13日

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  • Ruoyu Shi,
  • Yimeng Sang,
  • Christopher Ze Xin Chua,
  • Liuxiao Yang,
  • Jabed Iqbal,
  • Priscilla Wen Xian Loh,
  • Gaohua Wu,
  • Rongkui Luo,
  • Ye Xin Koh,
  • Jia Fan,
  • Qiang Gao,
  • Hongping Xia,
  • Jian Zhou,
  • Kai Zhu

摘要

Immune checkpoint inhibitor (ICI) based combined neoadjuvant/conversion therapy (NAT) is increasingly utilized in the management of initially unresectable intrahepatic cholangiocarcinoma (iCCA). However, immune-related pathologic response (irPR) features and immunotherapeutic response score (ITRS) remain poorly understood in iCCA.

This study enrolled 147 iCCA patients who received NAT. irPR features (tumor infiltrating lymphocyte, tertiary lymphoid structure, lymphoid aggregate, plasma cell infiltration, granuloma, neutrophil, foamy macrophage, cholesterol cleft, hemosiderin macrophage, giant cell, neovascularization and mature fibrosis) were accessed on routinely processed hematoxylin-eosin stained post-NAT surgical resection specimen tumor bed slides. Kaplan-Meier and Cox regression analyses were used to investigate irPR features and ITRS correlations with recurrence-free survival (RFS) and overall survival (OS).

The irPR features were identified in the post-NAT surgical resection specimen of iCCA. Six irPR features were included in ITRS. A binary ITRS scheme was developed, wherein patients classified as ITRS-low exhibited significantly better OS (hazard ratio [HR]:3.03; 95% confidence interval [CI]: 1.55–5.89, P < 0.01) and RFS (HR:1.94; CI: 1.24–3.03, P = 0.03) compared to those in the ITRS-high group, based on univariate analysis. In multivariate analysis including lymphovascular invasion, perineural invasion and major pathologic response, ITRS scheme was also found to be an independent prognostic factor for OS (HR: 1.95; 95% CI: 1.02–4.27, P = 0.04).

An irPR features-based ITRS scheme significantly predicts OS and RFS in post NA iCCA patients. The ITRS is feasible for implementation in routine diagnostic pathology practice and offers novel insights into resistance mechanisms associated with immunotherapy.