Abstract P2-14-11: Immune response monitoring in breast cancer patients treated with neoadjuvant chemotherapy combined with dendritic cell vaccines
Authors: Laura Hato, Susana Inogés, Belén Pérez, Luis Mejías, Rodrigo Sánchez-Bayona, Marta Santisteban, Ascensión López
Journal: Cancer Research (2022)

Abstract INTRODUCTION. Breast cancer (BC) is one of the most frequent cancers in women worldwide. Lack of therapeutic efficacy in some BC subtypes makes it necessary to develop new strategies. It is known that immune system plays a key role in the tumour control. Moreover, BC is immunogenic and the intensity of the immune response influences the clinical efficacy, and is correlated with a good prognosis. For that, manipulating the immune system to make it more effective could be an option. We design a clinical trial (NCT01431196) to evaluate the clinical efficacy of the combination of standard treatment with monocyte-derived dendritic cells vaccines preloaded with autologous tumour lysate (DCV) in stage I-III BC patients without HER2 overexpression. An in-depth immunological study was carried out. OBJECTIVES. To evaluate the immune response induced by the combination of neoadjuvant chemotherapy ± DCV ± radiation ± endocrine therapy in BC patients. METHODS. Serum and peripheral blood mononuclear cells (PBMCs) were collected from 20 luminal and triple negative BC patients before and after treatment. In serum, the presence of anti-tumour antibodies was studied by flow cytometry. PBMCs phenotype was evaluated by flow cytometry. In addition, functional studies were performed by incubating PBMCs with dendritic cells preloaded with autologous tumour lysate to evaluate specific immune response; specifically, T cell proliferation assay by [3H] thymidine incorporation and IFN-γ-producing cell assays by ELISPOT were done. Finally, the TCR clonality was assessed by flow cytometry. RESULTS. We identified IgG and IgM antibodies specific for breast cancer cell lines in the serum of 20 % and 40% of patients. Myeloid-derived suppressor cells decreased and NK cells increased with the treatment. Moreover, activation markers, such as HLADR, significantly increased in CD4+ and CD8+ lymphocytes after treatment, whereas PD1 and TIM3 decreased. In addition, an increase in the proliferation of specific T cells and in the number of IFN-γ producing cells after stimulation with tumor lysate pulsed DC was detected after treatment. Finally, very good clinical responders (pT4/5 with Miller&amp;Payne classification and pN0) had higher TCR diversity index (DI) in CD4+ and CD8+ T cells in pretreatment samples: in CD8+ T cells, diversity index decreased in both groups after treatment, with higher difference in the VGCR group. CONCLUSION. Our study provides strong support that combined treatment induce humoral and cellular immune responses. We observed an activation of the immune system and a decrease in some immune checkpoints and MDSC. Finally, patients with a higher TCR-DI initially have a better clinical response and treatment induced oligoclonal activation of T cells. Citation Format: Laura Hato, Susana Inogés, Belén Pérez, Luis Mejías, Rodrigo Sánchez-Bayona, Marta Santisteban, Ascensión López. Immune response monitoring in breast cancer patients treated with neoadjuvant chemotherapy combined with dendritic cell vaccines [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-11.