效应记忆细胞毒性 CD3(+)/CD8(+)/CD45RO(+) T 细胞预示三阴性乳腺癌患者生存良好且复发风险较低

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.