乳がん生存における免疫細胞の役割

タイトル: Spatially-resolved tumour infiltrating immune cells and prognosis in breast cancer

概要: BackgroundThe immune response in breast tumors has an important role in prognosis, but the role of spatial localization of immune cells and of interaction between subtypes is not well-characterized. We evaluated the association between spatially-resolved tissue infiltrating immune cells (TIICs) and breast cancer-specific survival (BCSS) in a large multi-center study. Patients and methodsTissue micro-arrays with tumor cores from 17,265 breast cancer patients of European descent were stained for CD8, FOXP3, CD20, and CD163. We developed a machine learning-based tissue-segmentation and immune cell detection algorithm using Halo to score each image for the percentage of marker-positive cells by compartment (overall, stroma, or tumor). We assessed the association between log transformed TIIC scores and BCSS using Cox regression. ResultsTotal CD8+ and CD20+ TIICs (stromal and intra-tumoral) were associated with better BCSS in women with ER-negative (HR per standard deviation = 0.91 [95% CI 0.85 - 0.98] and 0.89 [0.84 - 0.94] respectively) and ER-positive disease (HR = 0.92 [95% CI 0.87 - 0.98] and 0.93 [0.86 - 0.99] respectively) in multi-marker models. In contrast, CD163+ macrophages were associated with better BCSS in ER-negative disease (0.94 [0.87 - 1.00]) and a poorer BCSS in ER-positive disease 1.04 [0.99 - 1.10]. There was no association between FOXP3 and BCSS. The observed associations tended to be stronger for intra-tumoral than stromal compartments for all markers. However, the TIIC markers account for only 7.6 percent of the variation in BCSS explained by the multi-marker fully-adjusted model for ER-negative cases and 3.0 percent for ER-positive cases. ConclusionsThe presence of intra-tumoral and stromal TIICs is associated with better BCSS in both ER-negative and ER-positive breast cancer. This may have implications for the use of immunotherapy. However, the addition of TIICs to existing prognostic models would only result in a small improvement in model performance. HighlightsStromal and intra-tumoral CD8+ and CD20+ TIICs are associated with better survival in ER+ and ER-breast cancers. Stromal and intra-tumoral CD163+ TIICs are associated with better survival in ER- and poorer survival in ER+ breast cancers. The presence of FOXP3+ tissue infiltrating lymphocytes in breast tumors was not associated with survival in breast cancer.