256P - Protein signature of tertiary lymphoid structure predicts efficacy of neoadjuvant chemotherapy in triple-negative breast cancer

Background

Tertiary lymphoid structures (TLS), ectopic lymphocyte aggregates, have been identified as prognostic and predictive biomarkers in cancer. However, the clinical application of TLS-related protein signature in triple-negative breast cancer was less understood. This retrospective study on TLS signatures predicts the therapeutic efficacy of neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC) patients.

Methods

A total of 44 TNBC patients treated with anthracycline/taxane-based NACT were included. Core-needle biopsy specimens were used for 4D label-free quantitative proteomic analysis. Tumor microenvironment and differentially enriched pathways were evaluated via Gene Set Variation Analysis (GSVA).

Results

Of all patients, 19 (43.2%) achieved a pathologic complete response (pCR). Pathways related to interleukin, cytokines, Toll-like receptor, and extracellular matrix were enriched in the pCR patients, whereas metabolism- and AMPK-related pathways were enriched in the non-pCR patients. TLS score based on protein expression was evaluated by GSVA. TLS score was significantly higher in the pathologic complete response (pCR) group. Among the TLS-associated proteins, high expression of LAMP3 and CD3E was positively associated with NACT efficacy. Therefore, a novel two-gene signature (CD3E and LAMP3) was established to predict the pCR rate, which reached an astonishing 75% of pCR in the low-risk group (LAMP3 and CD3E high), the sensitivity, specificity, positive predictive value, and negative predictive value reaching 0.84, 0.63, 0.75, and 0.75, respectively. The low-risk group also displayed an anti-tumoral immunity profiling with increased multiple T cell subsets (CD8, Th2) and enriched IFN-γ activity.

Conclusions

TNBC patients with high TLS scores had better response to NACT and an inflamed immune microenvironment. A novel simplified TLS signature was proposed that could be used as a potential biomarker of the NATC for TNBC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Amoy Diagnostics Co., Ltd, Xiamen, China.

Disclosure

All authors have declared no conflicts of interest.