CD8 T 细胞空间生物标志物在 ER⁺ 与 ER⁻ 乳腺癌中的预后意义

Tumor Infiltrating Lymphocytes (TILs) have been shown to be prognostic in Triple-Negative Breast Cancer (TNBC), but are rarely considered in other subtypes, particularly estrogen receptor (ER) positive cancers (70-80% of breast cancers), due to lower TIL counts.

However, the spatial proximity of lower abundance TILs has not been evaluated in relation to breast cancer prognosis. In this study, multiplex immunofluorescent-stained images were used to identify cell types based on cytokeratin (Ck), CD8, and FoxP3 expression. Using distance-based visual morphometry between epithelial and immune cells, we computed new metrics, proximity and consistency , which capture spatial relationships between Ck+ tumor cells and CD8+ T-cells. Prognostic significance of proximity and consistency were compared to lymphocyte counts using log-rank tests. Worse relapse-free survival (RFS) was observed for both ER+ and ER- breast cancers with low proximity and consistency of CD8+ cells. Among ER negative breast cancers, proximity had the highest RFS hazard ratio (HR 1.

84, 95% CI [1. 18,2. 87]). Among ER positive participants, RFS hazard ratios for proximity and consistency were 2. 04 (95% CI [1. 39, 2. 98]) and 1. 82 (95% CI [1. 23, 2. 69]) respectively. These associations were stronger than those observed for lymphocyte count (HR 1. 35, 95% CI [0. 92,1. 98], log-rank p-value = 0. 13).

These IF-derived spatial metrics were also associated with established TILs metrics and RNA-based expression-based measures of tumor adaptive immune response. The prognostic significance of proximity in ER+ breast cancer implies that spatial parameters may identify individuals who would benefit from immune therapy; up to 75% of breast cancers experience T-cell proximity suggestive of immune susceptibility.