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:Tumor-Infiltrating Lymphocytes and Preoperative Partial Breast Irradiation in Early-Stage Breast Cancer: Insights From the Prospective PAPBI Cohort.
在这一接受术前部分乳腺照射的早期乳腺癌患者队列中,纵向评估显示RT后sTILs变化极小。在达到pCR的患者中,我们观察到其基线sTILs显著高于未达到pCR的患者。
目前对放射治疗(RT)与TIL(肿瘤浸润淋巴细胞)(TILs)之间相互作用的理解有限。我们研究了术前加速部分乳腺照射(PAPBI)对早期乳腺癌患者TILs的影响。此外,我们评估了基线TILs是否与RT的病理反应相关。
在前瞻性PAPBI试验中,早期乳腺癌患者接受术前RT(10×4或5×6 Gy),6周后行宽局部切除术。回顾性收集接受术后RT的匹配对照患者用于验证。按照既定指南,在诊断活检和切除标本的苏木精-伊红染色切片上手动评分间质TILs(sTILs)。使用Mann-Whitney U检验分析有无病理完全缓解(pCR)患者之间sTILs的基线差异,并使用线性混合模型评估sTILs的纵向变化。
共纳入72例PAPBI患者和68例匹配对照。在PAPBI队列中,基线sTILs普遍较低,中位数为2%(IQR,1%-2%)。8例患者(11%)达到pCR,这些患者的基线sTILs显著高于未达到pCR的患者(P = .021)。在64例具有可评估的放疗前和放疗后样本的PAPBI患者中,RT后观察到sTILs有轻微且无统计学意义的增加。对照患者的基线sTILs同样较低(中位数,2%;IQR,1%-2%),随时间未见显著变化。
PURPOSE: Current understanding of the interaction between radiation therapy (RT) and tumor-infiltrating lymphocytes (TILs) is limited. We investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on TILs in early-stage breast cancer patients. In addition, we evaluated whether baseline TILs were associated with pathologic response to RT. METHODS AND MATERIALS: In the prospective PAPBI trial, early-stage breast cancer patients received preoperative RT (10 × 4 or 5 × 6 Gy), followed by a wide local excision after 6 weeks. Matched control patients who underwent postoperative RT were retrospectively collected for validation. Stromal TILs (sTILs) were manually scored on hematoxylin- and eosin-stained slides from diagnostic biopsy and resection specimens, following established guidelines. Baseline differences in sTILs between patients with and without a pathologic complete response (pCR) were analyzed using the Mann-Whitney U test, and longitudinal changes in sTILs were evaluated with a linear mixed model. RESULTS: A total of 72 PAPBI patients and 68 matched controls were included. In the PAPBI cohort, baseline sTILs were generally low, with a median of 2% (IQR, 1%-2%). Eight patients (11%) achieved a pCR, and these patients had significantly higher baseline sTILs compared with patients without a pCR (P = .021). Among the 64 PAPBI patients with evaluable preirradiation and postirradiation samples, a minimal, nonsignificant increase in sTILs was observed following RT. Control patients had similarly low baseline sTILs (median, 2%; IQR, 1%-2%), with no significant changes over time. CONCLUSIONS: In this cohort of early-stage breast cancer patients receiving preoperative partial breast irradiation, longitudinal assessment showed minimal changes in sTILs after RT. In patients who achieved a pCR, we observed significantly higher baseline sTILs compared with those without a pCR.
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