Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 306-316 http://medscipublisher.com/index.php/cge 309 Limited studies suggest that MSI-high tumors may respond well to ICIs, but more research is needed to validate these findings in TNBC (Karn et al., 2020). The presence of tumor-infiltrating lymphocytes (TILs) has been shown to be a strong prognostic factor in TNBC. High levels of TILs are associated with better responses to ICIs and improved survival outcomes (Tomioka et al., 2017; Stanowska et al., 2022). For instance, patients with high TILs and high PD-L1 expression have shown significantly better disease-free survival (DFS) and overall survival (OS) compared to those with low TILs (Tomioka et al., 2017). TILs are currently being investigated as a potential biomarker to guide ICI therapy in TNBC (Blackley and Loi, 2019). 3.4 Integrated analysis of multiple biomarkers Given the limitations of individual biomarkers, integrated analysis of multiple biomarkers is being explored to enhance predictive accuracy. Combining TMB with immune gene expression profiles (GEP) or TILs has shown promise in predicting responses to ICIs more accurately than any single biomarker alone. For example, a study found that patients with both high TMB and high GEP had significantly higher pCR rates compared to those with low levels of both markers (Karn et al., 2020). Multifactorial models that incorporate PD-L1 expression, TMB, TILs, and other immune-related factors are likely to provide a more comprehensive assessment of ICI efficacy in TNBC (Zhang et al., 2021). Figure 2 Summary of immune cell features and dynamics in TNBC tumors (Adopted from Zhang et al., 2021) Image caption: (A) Characteristics and dynamics of key immune cell subsets following different treatments. Red (or green) arrows represent higher baseline levels predicting favorable (or unfavorable) responses, or the increase (or decrease) of immune cell subsets in responsive patients following treatment; (B) Immune features in responsive and nonresponsive tumors and their dynamics following different treatment regimens. TNBC tumors with substantial baseline CXCL13 T cells, B cells, and proinflammatory macrophages would show sensitivity, in contrast to resistance of TNBC tumors with substantial immunosuppressive macrophages, to the combination therapy. Paclitaxel regimen decreased while atezolizumab increased key antitumor immune cells in responsive tumors.+; (C) Potential crosstalk between CXCL13 T cells and their correlated immune cells inferred based on treatment-induced temporal dynamics. Expa, expansion; Migr, migration; Recr, recruitment (Adopted from Zhang et al., 2021)
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