Abstract 5799: The immune and metabolic profile in the response to neoadjuvant treatment with immune checkpoint inhibitors in triple-negative breast cancer patients
Authors: Lucía Serrano García, Guillermo Quintas, María Portero Hernández, David Collado Martínez, María Dolores Torregosa, Sara Marín, Mario Mancino, Jose Enrique O'Connor Blasco, Antonio Llombart-Cussac, María Leonor Fernández-Murga
Journal: Cancer Research (2025)

Abstract Background: Immune checkpoint inhibitors (ICIs) are a promising option for early triple negative breast cancer (TNBC) treatment, although not all the patients get good responses. The objective of the present work is to research immune and metabolic profiles through non-invasive methods that allow us to differentiate responders (R) and non-responders (NR) patients prior to receive neoadjuvant chemotherapy (NAC) with ICIs. Methods: 34 TNBC patients treated with NAC and ICIs were enrolled and blood samples were collected before treatment (baseline), after 3 weeks (3W) and at the end of treatment (Endpoint). Patients were classified as responders and non-responders based on whether they achieved histologically complete pathological response respectively after treatment. Cellular immune populations were characterized by flow cytometry. Metabolomic profile was determined by mass spectrometry. Results: We observed a significant increase in the percentage of total lymphocytes (p&amp;lt;0.001), Natural Killer T (NKT) cells (p=0.01) and CD8 T cells (p&amp;lt;0.001) throughout treatment for the total set of patients. When classified into response (R) and No-response (NR), only the R group obtained a significant increase in NKT (p&amp;lt;0.001) and CD8 T cells (p&amp;lt;0.001) after therapy. NR group showed higher percentages of Myeloid Derived Suppressor Cells (MDSCs) at all time points. These changes were statistically significant for total MDSCs (3W; p=0.03 and endpoint; p=0.01) and granulocytic-MDSCs at baseline (p=0.02) and endpoint (p=0.006). NR patients also had a significant increase of platelet to lymphocyte ratio (PLR) after treatment (p=0.017). Metabolomic analysis revealed differences in Tryptophan, cytochrome p450, arginine and proline, nicotine and nicotinamide and Lysine degradation pathways at baseline point between responses (p&amp;lt;0.05). At 3W the changes appeared in Tryptophan, steroid hormone biosynthesis, amino sugar and nucleotide sugar, bile acid, purine and cytochrome p450 pathways (p&amp;lt;0.05). Conclusion: Immunotherapy induced an activation of the immune system in patients with TNBC. This activation was more evident in patients in the R group, while in the NR groups had activated immunosuppression mechanisms such as MDSCs and PLR, which are associated with worse prognosis. Both groups of responses showed altered metabolites of different pathways that vary depending on the sample point. The changes observed between R and NR groups could allow establishing an immunosuppression mechanism in TNBC, as well as personalized patterns that predict the effectiveness of NAC with ICIs and help in clinical decision making. This investigation is still in the recruitment phase and metabolomic analysis of endpoint samples, hoping this tendency to continue. Citation Format: Lucía Serrano García, Guillermo Quintas, María Portero Hernández, David Collado Martínez, María Dolores Torregosa, Sara Marín, Mario Mancino, Jose Enrique O'Connor Blasco, Antonio Llombart-Cussac, María Leonor Fernández-Murga. The immune and metabolic profile in the response to neoadjuvant treatment with immune checkpoint inhibitors in triple-negative breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5799.