224P - Immunological Dynamics in Triple-Negative Breast Cancer: Peripheral Immune Responses to Neoadjuvant Therapy

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. In the KEYNOTE-522 trial (KN522), pembrolizumab plus neoadjuvant chemotherapy (nChT) in early TNBC improved pathological complete response (pCR) rates and event-free survival. However, its effect on peripheral blood immune responses remains unclear. This study aims to assess the impact of this association on immune populations, disease outcomes, and treatment toxicities.

Methods

Early-stage TNBC patients undergoing neoadjuvant therapy, according to the KN522, were recruited from 01/2024 to 06/2024. Comprehensive immunophenotyping was done by flow cytometry on peripheral blood, collected at three moments: before and after two and four treatment cycles. A control group of sex- and age-matched healthy donors was obtained from leukocyte depletion bags.

Results

Nine women were included, with a median age of 50 (36-64). Clinically, 89% (n=8) had T≥2 tumors, and 44% (n=4) had axillary lymph node involvement. In TNBC patients at baseline, we observed a disrupted immune response, with reduced T cell frequencies and increased activation markers in double negative, double positive, Th17, and Tc1 subsets. Additionally, Naïve B cells and natural killer (NK) cells decreased, while dendritic cells and myeloid-derived suppressor cells increased, indicating impaired immune surveillance. After two treatment cycles, the observed changes suggested early immune activation, with reduced mature B and activated regulatory T cells, and increased NK and activated CD4 T cells. After four cycles, the immune profile shifted to a Th1-dominant response, indicating a stronger anti-tumor activity. Two cases of grade ≥3 immune-mediated toxicity led to the discontinuation of immunotherapy, including hepatitis and colitis. Three patients underwent surgery, all achieving pCR.

Conclusions

Despite the small sample size, this real-world study showed a pattern of early immune activation with nCht associated with pembrolizumab, highlighting the potential of immunomonitoring to predict treatment response and support the rationale for other immune-focused neoadjuvant strategies. Further data will correlate immune dynamics with efficacy outcomes and safety profiles.

Legal entity responsible for the study

Laboratory of Immunology and Oncology, Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Portugal.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.