4.4 Article

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

Journal

DIGESTIVE DISEASES AND SCIENCES
Volume 66, Issue 2, Pages 474-482

Publisher

SPRINGER
DOI: 10.1007/s10620-020-06203-8

Keywords

Colorectal cancer; Liver metastasis; Immune microenvironment; Prognosis

Funding

  1. National Natural Science Foundation of China [NSFC: 81602066, 81772587]
  2. Natural Science Foundation of Guangdong Province [2016A030313280, 2018A030310260, 2014A030312015]
  3. Sci-Tech Foundation of Guangdong Province [2018YJ021]
  4. Medical Science Foundation of Guangdong Province [A2016023, 2018102516469945]
  5. Science and Technology Program of Guangdong [2015B020232008]
  6. Science and Technology Program of Guangzhou [15570006, 201508020250, 201510161726583, 201604020003]
  7. Guangdong Esophageal Cancer Institute Science and Technology Program [M201809]
  8. CSCO-HengRui Oncology Research Fund [Y-HR2018-184]
  9. third outstanding young talents training plan
  10. Medical Scientist program of Sun Yat-sen University cancer center
  11. Medical Science and Technology Research Fund Project of Guangdong Province [A2015003]

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The immune microenvironment differs between primary colon tumors and liver metastases, with more immunosuppressive cells in the liver potentially explaining why immunotherapy is less effective in colorectal cancer with liver metastases.
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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