基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Systemic immune mediators reflect tumour-infiltrating lymphocyte intensity and predict therapeutic response in triple-negative breast cancer.
Systemic immune mediators reflect tumour-infiltrating lymphocyte intensity and predict therapeutic response in triple-negative breast cancer.
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三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌。新辅助化疗已证实对其有效,且病理完全缓解(pCR)预示长期生存改善。免疫反应是新辅助化疗成功的关键,既往治疗前肿瘤组织样本中基质TIL(肿瘤浸润淋巴细胞)比例与实现pCR的可能性相关,体现了这一点。
本研究检测TNBC患者接受新辅助化疗前的全身免疫介质,评估全身免疫反应与TIL浸润强度、治疗反应和生存之间的关联。患者在手术时被分为pCR应答者或无应答者。
研究发现,与未达到pCR者相比,最终达到pCR的患者在治疗开始前具有更高水平的免疫介质,曲线下面积(AUC)为0.64–0.80。pCR应答者的炎症性全身免疫介质水平与TIL比例呈正相关。联合TIL和全身免疫介质水平后,AUC进一步提高(范围0.72–0.82)。
最后,对若干可预测pCR的全身细胞因子进行无进展生存期分析,根据这些细胞因子的高低产量将患者区分为生存较长和较短两组。本研究显示,在新辅助化疗开始前测得的循环细胞因子可预测TNBC患者是否达到pCR;此外,这些因子可作为高TIL浸润的替代标志物,或与TIL联合以更准确预测pCR和生存。
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC). Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumour-infiltrating lymphocytes (TILs) in pre-treated tumour tissue samples and the likelihood of achieving pCR.
Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery.
We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders versus non-pCR, with area under the curve (AUC) values of 0. 64-0. 80.
We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0. 72-0. 82). Last, performing a progression-free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long- and short-survival groups based on high and low production of the cytokines, respectively.
Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy.
Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.
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