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.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Spatial biomarkers of response to eribulin plus pembrolizumab in patients with metastatic triple negative breast cancer in the ENHANCE-1 trial.
我们的结果提示,有必要进一步研究除 T 细胞以外的免疫细胞群体作为 mTNBC 联合治疗的预测性生物标志物。
ENHANCE-1 是一项 Ib/II 期研究,评估 eribulin 联合 pembrolizumab 治疗转移性三阴性乳腺癌(mTNBC)。所有患者均有可测量病灶,且既往接受过最多 2 线全身治疗。我们识别出 142 例有可用样本的患者,并使用诊断性 H&E 以及 2 个抗体 panel 的多重免疫荧光评估治疗前肿瘤免疫微环境与缓解之间的关联。选择标志物以评估淋巴细胞和髓系细胞,包括:CD4、CD8、FoxP3、CD56、CD20、CD68、CD163、Vimentin 和 HLA-DR。虽然 H&E 评估的计算和人工评估的间质TIL(肿瘤浸润淋巴细胞)(sTILs)与缓解无关,但多重免疫荧光揭示了若干显著关联。这些包括在乳腺样本中,非缓解者间质 CD56+ 富集,以及非缓解者间质 CD4 + CD8+ 更高。缓解者表现出更高的间质巨噬细胞群体 CD68 +、CD68+Vimentin +、CD68 + CD163+Vimentin+,以及更高的间质 HLA-DR +。我们的结果提示,有必要进一步研究 T 细胞以外的免疫细胞群体作为 mTNBC 联合治疗的预测性生物标志物。
ENHANCE-1 was a phase Ib/II study which evaluated eribulin plus pembrolizumab as a treatment for metastatic triple negative breast cancer (mTNBC). All patients had measurable disease and up to 2 prior systemic treatments. We identified 142 patients with available samples and evaluated associations between the pre-treatment tumor-immune microenvironment and response using diagnostic H&Es and multiplexed immunofluorescence with 2 antibody panels. Markers were chosen to evaluate lymphocytes and myeloid cells including: CD4, CD8, FoxP3, CD56, CD20, CD68, CD163, Vimentin, and HLA-DR. While H&E-assessed computational and manual assessments of stromal tumor infiltrating lymphocytes (sTILs) did not associate with response, multiplex immunofluorescence revealed several significant associations. These include enrichment of stromal CD56+ in non-responders and higher stromal CD4 + CD8+ in non-responders in breast samples. Responders exhibited higher stromal macrophage populations CD68 + , CD68+Vimentin + , CD68 + CD163+Vimentin+ as well as higher stromal HLA-DR + . Our results suggest that further studies on immune cell populations other than T-cells as predictive biomarkers for combination therapies in mTNBC are warranted.
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