下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers.
An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers.
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NET 后 TILs 增加与 NET 反应不佳显著相关。鉴于 NET 后 TILs 增加的患者中 FOXP3+ T 细胞计数增加,而中性粒细胞计数并未减少,推测免疫抑制微环境的诱导在疗效较差中发挥了作用。这些数据可能部分表明免疫反应参与内分泌治疗的疗效。
雌激素受体(ER)阳性/人表皮生长因子受体2(HER2)阴性且TIL(肿瘤浸润淋巴细胞)(TILs)水平高的乳腺癌患者预后不良的原因尚不清楚。本研究探讨了TILs与新辅助内分泌治疗(NET)反应之间的关联。
我们招募了170例接受术前内分泌单药治疗的ER+/HER2-乳腺癌患者。评估NET前后的TILs,并记录其变化。此外,使用CD8和FOXP3免疫组化分析检查T细胞亚型。参考TIL水平或变化分析外周血中性粒细胞和淋巴细胞计数。应答者定义为治疗后Ki67表达水平2.7%。
治疗后(p = 0.016),而非治疗前(p = 0.464),TIL水平与NET的应答显著相关。在无应答者中,治疗后TIL水平显著升高(p = 0.001)。在TIL升高的患者中,治疗后FOXP3 + T细胞计数显著增加(p = 0.035),而在TIL未升高的患者中则无显著变化(p = 0.281)。在TIL未升高的患者中,治疗后中性粒细胞计数显著下降(p = 0.026),而在TIL升高的患者中则无显著变化(p = 0.312)。
The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.
We recruited 170 patients with ER + /HER2- breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels 2.7% after treatment.
Post-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312).
An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy.
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