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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.

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.