Prognostic value of various immune cells and Immunoscore in triple-negative breast cancer

Xinyu Ren; Yu Song; Junyi Pang; Longyun Chen; Liangrui Zhou; Zhiyong Liang; Huanwen Wu

doi:10.3389/fimmu.2023.1137561

Prognostic value of various immune cells and Immunoscore in triple-negative breast cancer

Front Immunol. 2023 Apr 6:14:1137561. doi: 10.3389/fimmu.2023.1137561. eCollection 2023.

Authors

Xinyu Ren¹, Yu Song², Junyi Pang¹, Longyun Chen¹, Liangrui Zhou¹, Zhiyong Liang¹, Huanwen Wu¹

Affiliations

¹ Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Abstract

Background: This study aimed to evaluate the expression status and prognostic role of various immunoregulatory cells and test in triple-negative breast cancer (TNBC).

Methods: The expression of five markers (CD3/CD4/CD8/CD19/CD163) of tumor immune cells was evaluated retrospectively in tumor sections from 68 consecutive cases of TNBC by immunohistochemistry. Computational image analysis was used to quantify the density and distribution of each immune marker within the tumor region, tumor invasive margin, and expression hotspots. Immunoscores were calculated using an automated approach. Other clinical characteristics were also analyzed.

Results: For all patients, Kaplan-Meier survival analysis showed that high CD3+ signals in the tumor region (disease-free survival (DFS), P=0.0014; overall survival (OS), P=0.0031) and total region (DFS, P=0.0014; OS, P=0.0031) were significantly associated with better survival. High CD4+ levels in the tumor region and total regions were significantly associated with better survival (P<0.05). For Hotspot analysis, CD3+ was associated with significantly better survival for all Top1, Top2, and Top3 densities (DFS and OS, P<0.05). High CD4+ levels were significantly associated with better prognosis for Top1 and Top3 densities (DFS and OS, P<0.05). For stage IIB and IIIC patients, CD3+ in the tumor region and all Top hotspots was found to be significantly correlated with survival (DFS and OS, P<0.05). CD4+ cells were significantly associated with survival in the tumor region, total region, and Top3 density (DFS, P=0.0213; OS, P=0.0728). CD8+ cells were significantly associated with survival in the invasive margin, Top2 density, and Top3 density. Spatial parameter analysis showed that high colocalization of tumor cells and immune cells (CD3+, CD4+, or CD8+) was significantly associated with patient survival.

Conclusion: Computational image analysis is a reliable tool for evaluating the density and distribution of immune regulatory cells and for calculating the Immunoscore in TNBC. The Immunoscore retains its prognostic significance in TNBC later than IIB stage breast cancer. Future studies are required to confirm its potential to predict tumor responses to chemotherapy and immune therapy.

Keywords: Immunoscore; image registration; immune microenvironment; immunohistochemical staining; triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Humans
Lymphocytes, Tumor-Infiltrating
Prognosis
Retrospective Studies
Triple Negative Breast Neoplasms*

Grants and funding

This study was funded by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-053). The funding source took no part in the design or conduct of the study.