Neoadjuvant chemotherapy modifies the immune status of tumor-draining lymph nodes of breast cancer patients: Implications for immunotherapy

NICOLÁS NÚÑEZ; LOIRAT D; DE LA ROCHERE P; NADAN A.T; SASTRE-GARAU X; MESEURE D; MILDER M; VIEL S; SEDLIK C; AMIGORENA S; PIAGGIO, ELIANE

Simposio; The European Cancer Congress. ECCO2015; 2015

Neoadjuvant chemotherapy modifies the immune status of tumor-draining lymph nodes of breast cancer patients: Implications for immunotherapyN. NUNEZ2 , D. LOIRAT1, , P. De La Rochere2, A.T. Nadan3, X. Sastre-Garau3, D. Meseure, M. Milder4, S. Viel2, C. Sedlik2, S. Amigorena4, E. Piaggio2.1Institut Curie, Medical Oncology, Paris, France.2Institut curie, Translational Immunotherapy Team- INSERM U932/Transfer Department, Paris, France.3Institut Curie, Pathology, Paris, France.4Institut Curie, INSERM U932, Paris, France.Background: Axillary lymph node metastasis and tumor infiltrating lymphocytes are prognostic factors for breast cancers (BC). Neoadjuvant chemotherapy (NAC) is a standard of care therapy for locally advanced BC. Only few studies have shown that chemotherapy can modify the tumor immune microenvironment. Tumor-draining lymph nodes (LNs) are the place of initiation of the adaptive immune response, and together with the tumor, represent potential sites of immunotherapy action. Recent data suggests that inhibitory immune checkpoint blockers, such as anti-PD-1/PD-L1 mAbs could represent an efficient treatment for metastatic BC. Of note, little is known about the impact of chemotherapy on the immune status of LNs. Here, we compared the distribution and phenotype of CD4+ and CD8+ T cell subsets between the LN from non-treated (NT) or NAC-treated BC patients.Material and Methods: 56 LNs from NT (HER2+=4, TN=3, Luminal=49) and 18 from NAC (HER2+=5, TN=3, Luminal=10) BC patients undergoing axillary surgery at Institut Curie Hospital were obtained in accordance with institutional ethical guidelines. Matched tumor samples (6 from NAC and 28 from NT patients) were also obtained. Samples were analyzed by multicolor flow cytometry. For statistical analysis, Mann?Whitney test were performed using Prism (GraphPadSoftware).Results: The proportion of CD4+ FOXP3high effector regulatory T cells (Tregs) was significantly increased in NAC compared to NT LNs (p