| Autor: |
Sun, Xiangjie, Zhai, Jie, Sun, Baohua, Parra, Edwin Roger, Jiang, Mei, Ma, Wencai, Wang, Jing, Kang, Anthony M., Kannan, Kasthuri, Pandurengan, Renganayaki, Zhang, Shanyu, Solis, Luisa Maren, Haymaker, Cara L., Raso, Maria Gabriela, Mendoza Perez, Julia, Sahin, Aysegul A., Wistuba, Ignacio I., Yam, Clinton, Litton, Jennifer K., Yang, Fei |
| Zdroj: |
Modern Pathology; 20210101, Issue: Preprints p1-8, 8p |
| Abstrakt: |
Triple-negative breast cancer (TNBC) with high tumour-infiltrating lymphocytes (TILs) has been associated with a promising prognosis. To better understand the prognostic value of immune cell subtypes in TNBC, we characterised TILs and the interaction between tumour cells and immune cell subtypes. A total of 145 breast cancer tissues were stained by multiplex immunofluorescence (mIF), including panel 1 (PD-L1, PD-1, CD3, CD8, CD68 and CK) and panel 2 (Foxp3, Granzyme B, CD45RO, CD3, CD8 and CK). Phenotypes were analysed and quantified by pathologists using InForm software. We found that in the ER-negative (ER <1% and HER2-negative) group and the ER/PR-low positive (ER 1–9% and HER2-negative) group, 11.2% and 7.1% of patients were PD-L1+by the tumour cell score, 29.0% and 28.6% were PD-L1+by the modified immune cell score and 30.8% and 32.1% were PD-L1+by the combined positive score. We combined ER-negative and ER/PR-low positive cases for the survival analysis since a 10% cut-off is often used in clinical practice for therapeutic purposes. The densities of PD-L1+tumour cells (HR: 0.366, 95% CI: 0.138–0.970; p= 0.043) within the tumour compartment and CD3+immune cells in the total area (tumour and stromal compartments combined) (HR: 0.213, 95% CI: 0.070–0.642; p= 0.006) were favourable prognostic biomarkers for overall survival (OS) in TNBC. The density of effector/memory cytotoxic T cells (CD3+CD8+CD45RO+) in the tumour compartment was an independent prognostic biomarker for OS (HR: 0.232, 95% CI: 0.086–0.628; p= 0.004) and DFS (HR: 0.183, 95% CI: 0.1301–0.744; p= 0.009) in TNBC. Interestingly, spatial data suggested that patients with a higher density of PD-L1+tumour cells had shorter cell-cell distances from tumour cells to cytotoxic T cells (p< 0.01). In conclusion, we found that phenotyping tumour immune cells by mIF is highly informative in understanding the immune microenvironment in TNBC. PD-L1+tumour cells, total T cells and effector/memory cytotoxic T cells are promising prognostic biomarkers in TNBC. |
| Databáze: |
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