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The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases

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Abstract

Background

The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported.

Methods

Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry. The prognostic role of the Immunoscore for relapse–free survival (RFS) and overall survival (OS) was analyzed with Kaplan–Meier curves and Cox multivariate models, and confirmed via an internal validation. Receiver operating characteristic (ROC) curves were plotted to compare the prognostic values of the Immunoscore and the clinical risk score (CRS) system.

Results

CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median RFS (95% confidence interval; 95% CI) 21.4 (7.8–35.1) vs. 8.7 (6.8–10.5) months, P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2–34.2) months, P < 0.001] than those with low Immunoscores (≤ 2). After stratification by CRS, the Immunoscore retained a statistically significant prognostic value for OS. The areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS were 0.711 [95% CI 0.642–0.781] and 0.675[95% CI 0.601–0.749] (P = 0.492), whereas the AUROC of the Immunoscore system for OS was larger than that of the CRS system [0.759 (95% CI 0.699–0.818) vs. 0.660 (95% CI 0.592–0.727); P = 0.029].

Conclusions

The Immunoscore of liver metastases can be applied to predict the prognosis of CRCLM patients following liver resection.

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Abbreviations

AUROC:

Area under the ROC curve

CAPEOX:

Oxaliplatin and capecitabine

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CRC:

Colorectal cancer

CRCLM:

Colorectal cancer liver metastases

CRS:

Clinical risk score

CT:

Center tumor

ESMO:

European society for medical oncology

FOLFIRI:

Irinotecan, 5-Fu and leucovorin

FOLFOX:

Oxaliplatin, 5-Fu and leucovorin

FOLFOXIRI:

Oxaliplatin, irinotecan, 5-Fu and leucovorin

GZMB:

Granzyme B

HAI:

Hepatic arterial infusion

HR:

Hazard ratio

IM:

Invasive margin

IQR:

Interquartile range

LV:

Leucovorin

OS:

Overall survival

RFS:

Relapse-free survival

ROC:

Receiver operating characteristic

TIL:

Tumor-infiltrating lymphocyte

Tregs:

T-regulatory cells

XELIRI:

Irinotecan and capecitabine

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Acknowledgements

We express our gratitude to all the patients for their participation in this study. We also appreciate all our colleagues at the Sun Yat-sen University Cancer Center who participated in administering the treatment in the current study. Medbanks (Beijing) Network Technology Co., Ltd. is thanked for data collection.

Funding

The work was supported by the Science and Technology Planning Project of Guangdong Province, China (201508020247).

Author information

Author notes

  1. Yun Wang and Hao-cheng Lin contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, 651# Dongfeng Road East, Guangzhou, 510060, People’s Republic of China

    Yun Wang, Hao-cheng Lin, Ma-yan Huang, Qiong Shao, Zhi-qiang Wang, Feng-hua Wang, Yun-fei Yuan, Bin-kui Li, De-shen Wang, Pei-rong Ding, Gong Chen, Xiao-jun Wu, Zhen-hai Lu, Li-ren Li, Zhi-zhong Pan, Peng Sun, Shu-mei Yan, De-sen Wan, Rui-hua Xu & Yu-hong Li

  2. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

    Yun Wang, Hao-cheng Lin, Zhi-qiang Wang, Feng-hua Wang, De-shen Wang, Rui-hua Xu & Yu-hong Li

  3. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

    Ma-yan Huang, Peng Sun & Shu-mei Yan

  4. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

    Qiong Shao

  5. Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

    Yun-fei Yuan & Bin-kui Li

  6. Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

    Pei-rong Ding, Gong Chen, Xiao-jun Wu, Zhen-hai Lu, Li-ren Li, Zhi-zhong Pan & De-sen Wan

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  1. Yun Wang
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Contributions

YL and RX were involved in the study design, protocol development, and data analysis and interpretation. MH and QS performed the immunohistochemical staining. SY and PS contributed to the Immunoscore evaluation. YW and HL performed the literature search for the study and were involved in data interpretation and writing the report. ZW, FW, YY, BL, DW, PD, GC, XW, ZL, LL, ZP and DW contributed to data collection. All authors reviewed and approved the manuscript for submission.

Corresponding authors

Correspondence to Rui-hua Xu or Yu-hong Li.

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Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Cite this article

Wang, Y., Lin, Hc., Huang, My. et al. The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases. Cancer Immunol Immunother 67, 435–444 (2018). https://doi.org/10.1007/s00262-017-2094-8

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  • DOI: https://doi.org/10.1007/s00262-017-2094-8

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