Decoding tumor-infiltrating lymphocytes heterogeneity in ductal carcinoma in situ: immune microenvironment dynamics and prognostic insights.

With the widespread use of mammography, the incidence of ductal carcinoma in situ (DCIS) has significantly increased and currently accounts for approximately 20-25% of newly diagnosed breast cancer cases. While a significant proportion of DCIS lesions exhibit long-term indolence without progression to invasive carcinoma, the current paucity of validated biomarkers for invasive potential prediction creates a therapeutic dilemma in clinical practice, potentially leading to either overtreatment of biologically inert lesions or undertreatment of high-risk precursors. Reflecting the body's adaptive immune response, tumor-infiltrating lymphocytes (TILs) have been demonstrated to be associated with adverse clinicopathologic factors in DCIS. The relationship between total TILs and the risk of DCIS recurrence remains controversial, but subpopulations of TILs such as FOXP3 + T lymphocytes, B cells, CD68, and CD163 macrophages are found to be associated with DCIS recurrence. Increased levels of total TILs are associated with increased malignancy of breast lesions, and the number and composition of TILs subpopulations change during DCIS progression. Moreover, dense TILs are correlated with high PD-L1 expression and the "healing" phenomenon in DCIS. Further exploration of the immune microenvironment, TILs subpopulations, and adaptive immune responses in DCIS remains a critical unmet need, contributing to more refined risk stratification of DCIS patients and facilitating the implementation of new treatments.