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:Changes in CD8-positive lymphocytes following chemotherapy with concomitant bevacizumab in HER2-negative breast cancer.
含贝伐珠单抗的化疗似乎可增强原发乳腺肿瘤中 CD8 阳性 TIL 的浸润,这可能有助于改善局部肿瘤消退和更好的治疗结局。
背景:贝伐珠单抗是一种抗血管生成药物,可抑制肿瘤血管形成,从而抑制肿瘤生长。TIL(肿瘤浸润淋巴细胞),尤其CD8阳性TIL,在抗肿瘤免疫应答中发挥关键作用。然而,贝伐珠单抗联合化疗对CD8阳性TIL动态变化的影响尚知之甚少。本研究旨在评估接受贝伐珠单抗联合化疗的晚期乳腺癌患者治疗前后CD8阳性TIL的变化。 方法:纳入30例最初无法手术、对一线含贝伐珠单抗化疗有应答并随后获得手术条件的晚期乳腺癌患者。通过免疫组化检测治疗前活检样本及治疗后手术标本中的CD8阳性TIL。根据其占间质TIL总量的比例,将间质CD8阳性TIL分为低、中、高水平。 结果:30例患者中,20例为Luminal样乳腺癌,10例为三阴性乳腺癌。治疗前,16例(64.0%)CD8阳性TIL表达较低,6例(24.0%)为中等,3例(12.0%)为高水平。治疗后,10例(33.3%)表达较低,11例(36.7%)为中等,9例(30.0%)为高水平,表明CD8阳性TIL水平增加。病理应答较高(病理应答分级≥2)的比例为36.7%;CD8阳性TIL增加的患者倾向于病理应答更好、总生存期更长,但差异未达到统计学显著性。相反,治疗后CD8阳性TIL高表达病例的ypT分期显著更低,提示贝伐珠单抗治疗后的免疫活化可能有助于局部肿瘤消退。 结论:含贝伐珠单抗化疗似乎可增强原发性乳腺肿瘤中的CD8阳性TIL浸润,可能有助于改善局部肿瘤消退及治疗结局。
BACKGROUND: Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy. METHODS: Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs. RESULTS: Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression. CONCLUSIONS: Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.
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