Prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Lujun Chen; Hao Huang; Ziyi Huang; Junjun Chen; Yingting Liu; Yue Wu; An Li; Junwei Ge; Zhang Fang; Bin Xu; Xiao Zheng; Changping Wu

doi:10.1186/s12957-023-03009-6

Prognostic values of tissue-resident CD8⁺T cells in human hepatocellular carcinoma and intrahepatic cholangiocarcinoma

World J Surg Oncol. 2023 Apr 6;21(1):124. doi: 10.1186/s12957-023-03009-6.

Authors

Lujun Chen^#^{1

2

3}, Hao Huang^#^{1

2

3}, Ziyi Huang^#^{4

5

6}, Junjun Chen^{1

2

3}, Yingting Liu^{1

2

3}, Yue Wu^{1

2

3}, An Li^{1

2

3}, Junwei Ge^{1

2

3}, Zhang Fang^{1

2

3}, Bin Xu^{1

2

3}, Xiao Zheng^{7

8

9}, Changping Wu^{10

11

12}

Affiliations

¹ Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
² Jiangsu Engineering Research Center for Tumor Immunotherapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
³ Institute of Cell Therapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
⁴ Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁵ Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, China.
⁶ Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, Soochow University, Suzhou, Jiangsu, China.
⁷ Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].
⁸ Jiangsu Engineering Research Center for Tumor Immunotherapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].
⁹ Institute of Cell Therapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].
¹⁰ Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].
¹¹ Jiangsu Engineering Research Center for Tumor Immunotherapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].
¹² Institute of Cell Therapy, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China. [email protected].

^# Contributed equally.

Abstract

Background: Tissue-resident CD8⁺T cells (CD103⁺CD8⁺T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the proliferation and effector function of tissue-resident CD103⁺CD8⁺T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8⁺T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated.

Methods: In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8⁺T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell-cell communication between tumor-infiltrating CD103⁺CD8⁺T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data.

Results: Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8⁺T cells in human HCC and ICC. Elevated CD8⁺T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8⁺T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103⁺CD8⁺T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8^highCD103^high had a better OS, and the CD8^lowCD103^low group tended to have a poorer prognosis in ICC. Evaluation of the CD103⁺CD8⁺T-cell ratio in CD8⁺T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103⁺CD8⁺T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103⁺CD8⁺T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion.

Conclusion: The CD103⁺ tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103⁺CD8⁺T cells might be helpful in assessing the on-treatment response of liver cancer.

Keywords: Hepatocellular carcinoma; Intrahepatic Cholangiocarcinoma; Multicolor immunohistochemistry; Prognosis; Tissue-resident CD103+CD8+T cells.

MeSH terms

Bile Duct Neoplasms* / pathology
Bile Ducts, Intrahepatic / pathology
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / pathology
Carcinoma, Hepatocellular* / pathology
Cholangiocarcinoma* / pathology
Humans
Liver Neoplasms* / pathology
Lymphocytes, Tumor-Infiltrating
Prognosis