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:Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.
Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.
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肝脏是乳腺癌(BC)转移的第三常见器官。肝转移(LM)主要有两种组织病理学生长模式(HGP):促纤维增生型和替代型。尽管有报道称肝转移患者免疫治疗疗效降低,但乳腺癌肝转移(BCLM)中的TIL(肿瘤浸润淋巴细胞)尚未得到研究。
本研究评估BCLM中的HGP和TIL分布及其与临床病理变量和生存的关系。研究收集了手术切除BCLM样本(133例患者,568张H&E切片)和尸检来源BCLM样本(23例患者,97张H&E切片)。HGP依据肿瘤与肝脏交界面的比例评估,并分为纯替代型(“纯r-HGP”)或任何促纤维增生型(“任何d-HGP”)。TIL按LM专用指南评分。采用Cox回归分析其与无进展生存期(PFS)和总生存期(OS)的关联。手术样本中“任何d-HGP”更常见(56%),尸检样本中“纯r-HGP”更常见(83%)。在手术队列中,除原发肿瘤侧别(p=0.049)和肝手术前全身治疗(p=0.039)外,未观察到HGP与临床病理特征的关联。与“任何d-HGP”相比,“纯r-HGP”中的TIL较少(p=0.001)。多变量分析中,“纯r-HGP”预示较差的PFS(HR 2.65;置信区间:1.45–4.82;p=0.001)和OS(HR 3.10;置信区间:1.29–7.46;p=0.011)。
总之,与任何促纤维增生型相比,纯替代型BCLM伴随较少TIL且结局更差。这些发现提示,HGP可用于进一步优化治疗方案。
Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM.
Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival.
We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP').
We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions.
We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0. 049) and the systemic preoperative treatment before liver surgery (p value = .
039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0. 001). 'Pure r-HGP' predicts worse PFS (HR: 2. 65; CI: (1. 45-4. 82); p value = 0. 001) and OS (HR: 3. 10; CI: (1. 29-7. 46); p value = 0. 011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'.
These findings suggest that HGP could be considered to refine treatment approaches.
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