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Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis

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Abstract

Background

Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood.

Patients and Methods

Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon’s signed rank test.

Results

All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069).

Conclusions

The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.

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Acknowledgments

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Funding

This study was supported by National Natural Science Foundation of China (NSFC: 81602066 and 81772587); Natural Science Foundation of Guangdong Province (2016A030313280 and 2018A030310260); The Sci-Tech Foundation of Guangdong Province (2018YJ021); The Medical Science Foundation of Guangdong Province (A2016023 and 2018102516469945). Natural Science Foundation of Guangdong Province (Grant Number 2014A030312015), Science and Technology Program of Guangdong (Grant Number 2015B020232008), Science and Technology Program of Guangzhou (Grant Numbers 15570006, 201508020250, 201510161726583, 201604020003), Guangdong Esophageal Cancer Institute Science and Technology Program (Grant Number M201809), CSCO-HengRui Oncology Research Fund (Grant Number Y-HR2018-184), the third outstanding young talents training plan and Medical Scientist program of Sun Yat-sen University cancer center, Medical Science and Technology Research Fund Project of Guangdong Province (Grant Number A2015003).

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Authors and Affiliations

  1. Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Su-Na Zhou, Wen-Tao Pan, Meng-Xian Pan, Qiu-Yun Luo, Lin Zhang, Xiang-Lei Yan, Lu-Ping Yuan, Yu-Xin Zhang, Da-Jun Yang & Miao-Zhen Qiu

  2. Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Lin Zhang

  3. Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Jun-Zhong Lin & Yu-Jie Zhao

  4. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China

    Miao-Zhen Qiu

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  1. Su-Na Zhou
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Contributions

Conception and design of this study were carried out by MZQ, DJY, and LZ, QYL, MXP and SNZ. WTP conducted most part of the experiments, analyzed the data and wrote the manuscript. XLY, LPY and YXZ preformed the immunofluorescence. JZL, and YJZ collected the clinical data.

Corresponding author

Correspondence to Miao-Zhen Qiu.

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No potential conflict of interest was disclosed.

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All experiments were performed under the guidance of Sun Yat-Sen University Ethics Committee.

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All the authors have read and approved the manuscript.

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Data are available when request.

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Zhou, SN., Pan, WT., Pan, MX. et al. Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis. Dig Dis Sci 66, 474–482 (2021). https://doi.org/10.1007/s10620-020-06203-8

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  • DOI: https://doi.org/10.1007/s10620-020-06203-8

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