Breast cancer microenvironment composition associated with high PD-L1 expression

A key challenge that complicates early diagnosis, choice of treatment tactics, and prognosis of the course of breast cancer (BC) is its heterogeneity. Today, many researchers focus on the TME as an environment that directly determines the development and progression of BC. Given this, it is necessary to deepen our understanding of the features of the TME and its interaction with tumor cells.

to characterize the cellular and molecular composition of the TME in early-stage BC, stratified by PD-L1 expression status, with a focus on immune cell infiltration (CD68 + and CD163 + cells, mast cells (MCs)), cytokine profiles (IL-6, IL-10 and TNF-α), and extracellular matrix (vimentin (VIM), TGF-β1, collagen type 1 alpha 1 chain (COL1A1), collagen type 3 alpha 1 chain (COL3A1), matrix metalloproteinases (MMP) both collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), lysyl oxidase (LOX), and Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD, to identify features associated with an immunosuppressive and tumor-promoting phenotype.

The study was conducted on the postoperative material of 124 patients with stage I-II BC. The expression of TME markers was analyzed immunohistochemically. The mRNA gene expression was estimated using the real-time RT-PCR method. Serum cytokines levels were assessed by the ELISA method.

We found an association between high PD-L1 expression and increased levels of infiltration of BC tissue with CD163 + macrophages and MCs by 2.9 and 2.5 times, respectively. At the same time, it was shown that BC with high PD-L1 expression is characterized by a significant increase in serum interleukin-10 (IL-10) levels against the background of decreasing the interleukin-6 (IL6) levels. Simultaneously, high PD-L1 expression is associated with a 2.13-fold increase in transforming growth factor-β1 (TGF-β1) and a 13.24% increase in collagen type 1 (COL1A1). Simultaneously, in ВС with high levels of PD-L1 expression, we found the expression elevations of collagenases (MMP-1, MMP-8, and MMP-13 by 2.43, 1.80, and 1.73 times, respectively), gelatinases (MMP-2 and MMP-9 by 2.03 and 2.05 times, respectively), and collagen density regulatory protein lysyl oxidase (LOX) (by 2.48 times, respectively).

High PD-L1 expression in BC tissue is associated with features of an immunosuppressive TME, including increased infiltration of immune cells with pro-tumorigenic properties, alterations in the cytokine profile, and remodeling of the stromal matrix.