174P - Prognostic value of the immune and metabolic profile in the response to neoadjuvant treatment with ICIs in triple-negative breast cancer patients (TNBC)

Background

Immune checkpoint inhibitors (ICIs) are showing promising results in TNBC, although there is a percentage of patients who do not respond to therapy. The objective of this work is to research through non-invasive methods immune cellular and metabolic profiles that allow us to predict a complete (CR) or a partial response (PR).

Methods

24 TNBC patients treated with neoadjuvant ICIs plus chemotherapy were included and samples were taken before the treatment (baseline), after 3 weeks (3W) and preoperative (preop). Immunophenotyping panels were performed using flow cytometry and the cytokines production was studied by ELISA. In addition, the metabolomic profile was analyzed by mass spectrometry.

Results

There was a significant increase in the percentage of total lymphocytes (p<0.001), NKT cells (p=0.01) and CD8+ (p<0.001) after the treatment (24-30 weeks), for the total set of patients. A positive correlation between the NKT cells and the levels of perforin A was observed (rho=0.9). The rise in NKTs was only statistically significant in RC (p=0.005). PR patients showed higher levels than CR of all the myeloid suppressor cell subpopulations (MDSCs) before treatment. This difference was statistically significant for total MDSCs (3W; p=0.04 and preop; p=0.02) and mainly in granulocytic MDSCs (G-MDSCs) at 3W (p=0.03). Results obtained revealed statistically significant altered metabolic pathways in the basal point including the Purine, Pyrimidine, and Tryptophan metabolisms. The analysis of 3W samples showed a different set of altered metabolic pathways including Lysine degradation, and Inositol phosphate metabolism (p<0.05).

Conclusions

Immunotherapy treatment is able to trigger an activation of the immune system especially in patients who respond completely to treatment. Those who respond partially present activated immunosuppression mechanisms, such as MDSCs. This, added to the differences of the metabolomic profile of each response, allows us to establish personalized patrons that predict the effectiveness of the ICIs therapy in TNBC and can help in clinical decision making. This work is still in the recruitment and metabolomic analysis phase, expecting this tendency to continue.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

ISS CARLOS III.

Disclosure

All authors have declared no conflicts of interest.