Santisteban Marta, Solans Belén Pérez, Hato Laura, Urrizola Amaia, Mejías Luis Daniel, Salgado Esteban, Sánchez-Bayona Rodrigo, Toledo Estefanía, Rodríguez-Spiteri Natalia, Olartecoechea Begoña, Idoate Miguel Angel, López-Díaz de Cerio Ascensión, Inogés Susana
Department of Medical Oncology, Clínica Universidad de Navarra, Avda. Pío XII 36, 31008 Pamplona, Spain.
IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
Ther Adv Med Oncol. 2021 Dec 23;13:17588359211064653. doi: 10.1177/17588359211064653. eCollection 2021.
Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients.
Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy.
The tpCR rate was 28.9% in the VG and 9.09% in the CG ( = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% 30.7% ( = 0.25), 16.6% 0% in luminal B ( = 0.15), and none among luminal A patients in VG CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population ( < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG ( < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment.
The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome.
ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.
原发性乳腺癌（BC）的免疫浸润高于转移性疾病，这为免疫治疗提供了理想的治疗场景。最近，新辅助化疗（NAC）联合免疫检查点抑制剂已证明可提高BC患者的病理完全缓解率（tpCR）。我们研究的目的是评估在HER2阴性BC患者中，将树突状细胞疫苗（DCV）添加到NAC中的安全性、可行性和疗效。
39例早期BC患者在接受NAC的同时接受DCV，组成疫苗接种组（VG），并与44例患者作为对照组（CG）进行比较。所有患者均接受基于蒽环类药物和紫杉烷类的NAC（ddECx4→Dx4），随后进行手术±放疗±激素治疗。
VG组的tpCR率为28.9%，CG组为9.09%（P = 0.03）。三阴性（TN）BC的病理CR率分别为50.0%和30.7%（P = 0.25），腔面B型为16.6%和0%（P = 0.15），VG组和CG组的腔面A型患者均无病理CR。DCV对程序性细胞死亡配体1（PD-L1）阴性人群的影响显著更高（P < 0.001）。与CG组相比，VG组残留疾病患者的PD-L1表达增加（P < 0.01）。未发生≥3级疫苗相关不良事件。中位随访8年，无病生存率或总生存率未见变化。在骨髓来源的抑制细胞（MDSC）、自然杀伤细胞（NK）和T细胞中观察到DCV后外周血的表型变化。VG组分别有69%和74%的患者检测到血细胞增殖增加和干扰素（IFN）-γ产生增加。还发现了体液反应。67%的患者检测到TCR-β库的克隆性变化，治疗后多样性指数下降。
DCV联合NAC是安全的，可提高tpCR，对PD-L1阴性肿瘤有显著益处。DCV改变肿瘤微环境，并在外周血中产生细胞和体液反应，对预后无影响。
ClinicalTrials.gov编号：NCT01431196。EudraCT 2009-017402-36。
