New research findings highlight the crucial role of immune biomarkers in predicting treatment outcomes for triple-negative breast cancer (TNBC), offering potential guidance for more personalized therapeutic approaches.
TILs as Prognostic Indicators
Dr. Roberto Salgado from the Peter MacCallum Cancer Centre reports that high levels of tumor-infiltrating lymphocytes (TILs) serve as reliable indicators of active antitumor immune response. A comprehensive retrospective analysis revealed that TNBC patients with TIL levels ≥50% achieved impressive 5-year distant relapse-free survival rates of 94%, compared to 78% in patients with TIL levels below 30%.
The prognostic value of TILs extends to immunotherapy responses. In the phase III KEYNOTE-119 study, patients with TIL levels ≥5% demonstrated superior outcomes with pembrolizumab treatment, achieving median overall survival of 12.5 months compared to 11.3 months with chemotherapy.
Immunotherapy Response Patterns
The IMPASSION130 study further validated the importance of immune biomarkers, showing enhanced survival benefits in patients receiving atezolizumab plus nab-paclitaxel when both PD-L1 expression and TIL levels were high. Notably, the BELLINI study reported that one-third of early-stage TNBC patients with TIL levels ≥50% achieved complete pathologic response with nivolumab plus ipilimumab treatment, enabling them to avoid adjuvant chemotherapy.
Emerging Biomarker Landscape
Dr. Justin Balko of Vanderbilt-Ingram Cancer Center emphasizes the importance of identifying resistance markers rather than focusing solely on sensitivity indicators. His research highlights Major Histocompatibility Complex Class II (MHC-II) as a promising pan-cancer biomarker, with its presence on tumor cells correlating with improved immunotherapy outcomes.
The KEYNOTE-522 study's exploratory analysis revealed that high tumor mutational burden associates with improved event-free survival in patients receiving pembrolizumab plus chemotherapy. Additional promising biomarkers under investigation include B-cell markers, T follicular helper cells, and tertiary lymphoid structures.
Future Directions
Researchers are also exploring the potential role of the microbiome as both a predictive biomarker and therapeutic target. This emerging field suggests the possibility of microbiome transfer from responding to non-responding patients to enhance treatment outcomes.
The integration of these biomarkers into clinical practice could revolutionize TNBC treatment by enabling more precise patient selection for immunotherapy, potentially improving outcomes while minimizing unnecessary exposure to treatment-related toxicities.
