Role of tumor‑infiltrating lymphocytes and miR‑155 in breast cancer: Insights into carcinogenesis and their potential as prognostic biomarkers (Review)

Breast cancer is the most common cancer in the female population worldwide. The present review examines the biology of breast cancer, with a focus on the interplay between tumor‑infiltrating lymphocytes (TILs) and microRNAs (miRNAs or miRs). TILs, which reflect the immune system activity in combating tumors, are associated with more favorable prognoses and positive response to therapies. Elevated levels of TILs characterize lymphocyte‑predominant breast cancers (LPBCs), which are associated with higher therapeutic response rates in triple‑negative breast cancer, a type of LPBC. Defining the threshold for LPBCs presents a challenge: TIL levels ≥50% are associated with short‑term pathological complete response as well as long‑term overall and disease‑free survival; however, this percentage is not often achieved in clinical practice. Conversely, a lower threshold of 30% lymphocyte infiltration can predict favorable prognosis for anticancer therapy and allows for the identification of a broader range of patients. The tumor inflammatory landscape is regulated by miRNAs, particularly miR‑155. Elevated levels of miR‑155 are associated with the presence of TILs and a favorable inflammatory profile, leading to a tumor‑inflamed microenvironment. Moreover, miR‑155 is associated with various antitumoral immune cells, including CD8⁺ T cells and M1 macrophages, but negatively associated with pro‑tumoral regulatory T cells and M2 macrophages. Overexpression of miR‑155 results in an increase in the levels of the C‑X‑C chemokine ligands, constituted by two conserved cysteines separated by a different amino acid which bind to the same chemokine receptor CXC chemokine receptor 3. These results in activation of T cells a process that involves the inhibition of suppressor of cytokine signaling 1 and an elevated ratio of phosphorylated STAT1/STAT3. Additionally, miR‑155 affects key signaling pathways, including the PI3K/AKT and IL‑6/STAT3 pathways, and increases sensitivity to immune checkpoint blockade therapy. In clinical samples from patients with BC, serum levels of miR‑155 align with both tumor miR‑155 levels and the immune status of the tumor. The present review emphasizes the importance of understanding the dynamics between TILs and miRNAs to identify new prognostic and predictive biomarkers, proposing a more integrated and personalized approach in the management of BC.