HR+ 유방암 내의 단핵구와 대식세포에서의 SPP1 발현과 종양침윤림프구의 관련성

Abstract

Breast cancer is a globally prevalent cancer, categorised into hormone receptor-positive (HR+), HER2- positive (HER2+), and triple-negative (TNBC) subtypes. The level of tumour-infiltrating lymphocytes (TILs) is an important prognostic indicator of breast cancer. To explore the divergent roles of TIL levels across various subtypes and examine their effect on immune cell composition and tumour microenvironment, we employed single-cell RNA sequencing on 31 patients with breast cancer exhibiting different TIL levels and subtypes. We observed elevated SPP1+ macrophages and reduced mucosal-associated invariant T cells in HR+ breast cancer with high TIL levels (TIL high HR+ breast cancer). Furthermore, SPP1 expression was increased in other monocytes and macrophages (mono/macro) subgroups in TIL high HR+ breast cancer. Both SPP1+ macrophages and TIL high HR+ breast cancer mono/macro showed increased expression of genes related to ECM remodeling. Moreover, cell-cell interaction analyses revealed enhanced SPP1 signalling in the interaction between mono/macro and T cells in TIL high HR+ breast cancer compared to TIL low group. Spatial transcriptomics data of HR+ breast cancer highlighted close proximity of mono/macro, CD8+ T cells, and CD4+ T cells in TIL high HR+ breast cancer compared to TIL low group. Collectively, we discovered a novel role of SPP1-expressing mono/macro in influencing T cells within the tumour microenvironment of TIL high HR+ breast cancer. Our findings may explain poor prognosis of HR+ breast cancer associated with elevated TIL levels, suggesting that SPP1+ macrophages could be potentially targeted to improve their prognosis. Keywords: Breast cancer, Hormone receptor (HR), Tumour-infiltrating lymphocytes, Tumour- associated macrophages, Secreted Phosphoprotein 1