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Clinical Studies

The prognostic value of tumour-infiltrating lymphocytes, programmed cell death protein-1 and programmed cell death ligand-1 in Stage I–III triple-negative breast cancer

British Journal of Cancer volume 128, pages 2044–2053 (2023)Cite this article

Subjects

Abstract

Background

Tumour-infiltrating lymphocytes (TILs) represent a robust biological prognostic biomarker in triple-negative breast cancer (TNBC); however, the contribution of different subsets of immune cells is unclear. We investigated the prognostic value of immune markers, including stromal TILs (sTILs), CD8+T and FOPX3+T cells, PD-1 and PD-L1 in non-metastatic TNBC.

Methods

In total, 259 patients with Stage I–III TNBC were reviewed. The density of sTILs along with the presence of total (t), stromal (s), and intratumoral (i) CD8+T cells and FOPX3+T cells were evaluated by haematoxylin and eosin and immunohistochemical staining. Immunohistochemical staining of PD-1, PD-L1 was also conducted.

Results

All immune markers were positively correlated with each other (P < 0.05). In the multivariate analysis, sTILs (P = 0.046), tCD8+T cells (P = 0.024), iCD8+T cells (P = 0.050) and PD-1 (P = 0.039) were identified as independent prognostic factors for disease-free survival (DFS). Further analysis showed that tCD8+T cells (P = 0.026), iCD8+T cells (P = 0.017) and PD-1 (P = 0.037) increased the prognostic value for DFS beyond that of the classic clinicopathological factors and sTILs.

Conclusions

In addition to sTILs, inclusion of tCD8+T, iCD8+T cells, or PD-1 may further refine the prognostic model for non-metastatic TNBC beyond that including classical factors alone.

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Fig. 1: Representative microphotographs (×200) of the stroma and tumour nest.
Fig. 2: Kaplan–Meier curves stratified by sTILs expression.

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Data availability

All data generated and analysed during this study are included in this article (and its supplementary information files).

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Acknowledgements

We express our heartfelt gratitude to Ms. Xiu-Yun Liu, Ms. Bo Zheng and Ms. Lei Guo from the Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College for their invaluable technical support throughout the course of this project. Their expertise and guidance were essential in making this work a reality.

Funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (2020-I2M-C&T-B-075, 2021-I2M-1-014) and the National Natural Science Foundation of China (81972860).

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  1. These authors contributed equally: Guang-Yi Sun, Jing Zhang, Bing-Zhi Wang.

Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China

    Guang-Yi Sun, Hao Jing, Hui Fang, Yu Tang, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Yuan Tang, Shu-Nan Qi, Bo Chen, Ning-Ning Lu, Ning Li, Ye-Xiong Li & Shu-Lian Wang

  2. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China

    Jing Zhang, Bing-Zhi Wang & Jian-Ming Ying

  3. Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 350014, Fuzhou, China

    Jing Zhang

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Contributions

G-YS: formal analysis, investigation, data collection, methodology and writing of the original draft. JZ: formal analysis, investigation, data collection, methodology and writing of the original draft. B-ZW: formal analysis, investigation, data collection, methodology and writing of the original draft. HJ: patient care and review and editing of the manuscript. HF: patient care and review and editing of the manuscript. Yu Tang: patient care and review and editing of the manuscript. Y-WS: patient care and review and editing of the manuscript. JJ: patient care and review and editing of the manuscript. Y-PL: patient care and review and editing of the manuscript. Yuan Tang: patient care and review and editing of the manuscript. S-NQ: patient care and review and editing of the manuscript. BC: patient care and review and editing of the manuscript. N-NL: patient care and review and editing of the manuscript. NL: patient care and review and editing of the manuscript. Y-XL: formal analysis and data collection, validation, statistical analysis guidance, and project administration, patient care, and writing and editing of the first draft of the manuscript. J-MY: formal analysis and data collection, validation, statistical analysis guidance, project administration, patient care and writing and editing of the first draft of the manuscript. S-LW: formal analysis and data collection, validation, statistical analysis guidance, project administration, patient care and writing and editing of the first draft of the manuscript.

Corresponding authors

Correspondence to Ye-Xiong Li, Jian-Ming Ying or Shu-Lian Wang.

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The study was approved by the Institutional Review Board of Cancer Hospital, the Chinese Academy of Medical Sciences and Peking Union Medical College (approval number 15-057/984) and was conducted according to the Declaration of Helsinki. The requirement of informed consent was waived.

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Sun, GY., Zhang, J., Wang, BZ. et al. The prognostic value of tumour-infiltrating lymphocytes, programmed cell death protein-1 and programmed cell death ligand-1 in Stage I–III triple-negative breast cancer. Br J Cancer 128, 2044–2053 (2023). https://doi.org/10.1038/s41416-023-02218-w

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