Modification of Breast Cancer Milieu with Chemotherapy plus Dendritic Cell Vaccine: An Approach to Select Best Therapeutic Strategies
Luis Mejías Sosa,
Álvaro López-Janeiro,
Alicia Córdoba Iturriagagoitia,
Pablo Sala,
Belén P. Solans,
Laura Hato,
Susana Inogés,
Ascensión López-Díaz de Cerio,
Francisco Guillén-Grima,
Jaime Espinós,
Susana De La Cruz,
María Dolores Lozano,
Miguel A Idoate,
Marta Santisteban
Affiliations
Luis Mejías Sosa
Department of Pathology, Hospital Universitario Rey Juan Carlos, Gladiolo, 28933 Madrid, Spain
Álvaro López-Janeiro
Department of Pathology, Clínica Universidad de Navarra, Pío XII 14 Avenue 36, 31008 Pamplona, Spain
Alicia Córdoba Iturriagagoitia
Department of Pathology, Complejo Hospitalario de Navarra, Irunlarrea 3, 31008 Pamplona, Spain
Pablo Sala
Department of Medical Oncology, Breast Cancer Unit, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Belén P. Solans
Pharmacometrics and Systems Pharmacology, Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy and Nutrition, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Laura Hato
Cell Therapy Unit, Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Susana Inogés
Cell Therapy Unit, Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Ascensión López-Díaz de Cerio
Cell Therapy Unit, Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Francisco Guillén-Grima
Department of Preventive Medicine, Universidad de Navarra, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Jaime Espinós
Department of Medical Oncology, Breast Cancer Unit, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Susana De La Cruz
Department of Medical Oncology, Complejo Hospitalario de Navarra, Irunlarrea 3, 31008 Pamplona, Spain
María Dolores Lozano
Department of Pathology, Clínica Universidad de Navarra, Pío XII 14 Avenue 36, 31008 Pamplona, Spain
Miguel A Idoate
Department of Pathology, Clínica Universidad de Navarra, Pío XII 14 Avenue 36, 31008 Pamplona, Spain
Marta Santisteban
Department of Medical Oncology, Breast Cancer Unit, Clínica Universidad de Navarra, Pío XII Avenue 36, 31008 Pamplona, Spain
Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). This enrichment was seen in up to 67% of TNBC patients in the experimental arm as compared with the CG (20%). An association between CD8 TILs before NAC (4% cut-off point) and pathological complete response in the VG was found in the univariate and multivariate analysis (OR = 1.41, IC95% 1.05–1.90; p = 0.02, and OR = 2.0, IC95% 1.05–3.9; p = 0.03, respectively). Conclusion: Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC.
