Insitute of Medical Immunology, Martin Luther University Halle Wittenberg, Halle, Sachsen-Anhalt, Germany.
Department of Obstetrics and Gynecology, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany.
J Immunother Cancer. 2020 Nov;8(2). doi: 10.1136/jitc-2020-001261.
Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with surgery and chemotherapy. Since TNBC is also considered the most immunogenic type of BC with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients' survival, many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease. In order to efficiently combine chemotherapy with immunotherapy, it is important to evaluate the effect of chemotherapy on immune cells in vivo.
Peripheral blood was taken from 56 patients with TNBC undergoing neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel (Nab-Pac) followed by epirubicin and cyclophosphamide (EC) at three different time points. Multicolor flow cytometry was used to characterize the immune cell composition and functional properties along neoadjuvant chemotherapy.
Whereas the first phase of the neoadjuvant chemotherapy did not significantly alter the patients' immune cell composition, after the second phase of chemotherapeutic administration most B cells (>90%) were lost and the frequency of natural killer (NK) cells and CD4 T lymphocytes decreased approximately to 50%. In contrast, the frequency of CD8 T cells were less affected.
Despite late consequences of Nab-Pac cannot be ruled out, these data suggest that different chemotherapeutics might have distinct effects on the immune cell repertoire and that different immune cell populations exhibit a specific susceptibility to these chemotherapies with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies.
NCT02685059.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌（BC）形式。由于缺乏 HER2 或激素受体等靶点，早期 TNBC 采用手术和化疗治疗。由于 TNBC 也被认为是最具免疫原性的 BC 类型，肿瘤浸润淋巴细胞可预测化疗反应，并对患者的生存预后有预测作用，因此目前正在临床试验中探索许多不同的免疫治疗策略来治疗这种疾病。为了有效地将化疗与免疫治疗相结合，评估化疗对体内免疫细胞的影响非常重要。
从 56 名接受纳米白蛋白结合紫杉醇（Nab-Pac）联合表柔比星和环磷酰胺（EC）新辅助化疗的 TNBC 患者中采集外周血，在三个不同时间点进行。多色流式细胞术用于描述新辅助化疗过程中免疫细胞组成和功能特性的变化。
尽管新辅助化疗的第一阶段并没有显著改变患者的免疫细胞组成，但在第二阶段化疗后，超过 90%的 B 细胞丢失，自然杀伤（NK）细胞和 CD4 T 淋巴细胞的频率下降约 50%。相比之下，CD8 T 细胞的频率受影响较小。
尽管不能排除 Nab-Pac 的晚期影响，但这些数据表明不同的化疗药物可能对免疫细胞库有不同的影响，不同的免疫细胞群体对这些化疗药物具有特定的易感性，B 细胞和 NK 细胞比 T 细胞更容易受到影响。这也可能对化疗与免疫治疗的联合治疗产生影响。
NCT02685059。
