JAMA肿瘤学:黑蝴蝶型乳腺癌复发元凶,可能系免疫反应减弱
2016/01/06
作为“粉红丝带上的黑蝴蝶”,HER2阳性乳腺癌是乳腺癌分型中较为危险的一种亚型。相比于其他类型的乳腺癌,HER2阳性有着着病情恶化更快、转移复发概率更高的坏预兆。最新研究表明,HER2性乳腺癌复发可能是因为抗HER2免疫反应减弱。


过去几年,科学家已经在癌症治疗的诊断方法、治疗新药方面取得了不少重大进展。然而,由于肿瘤本身包含复杂的异质化,所以完全根除癌变细胞,尤其是乳腺癌,仍然是一个重大挑战。

其中,由以HER2阳性乳腺癌最为凶险。作为“粉红丝带上的黑蝴蝶”,HER2阳性乳腺癌是乳腺癌分型中较为危险的一种亚型。相比于其他类型的乳腺癌,HER2阳性有着着病情恶化更快、转移复发概率更高的坏预兆。对其最常用的药物是赫赛汀。

近期,来自于宾夕法尼亚大学佩雷尔曼医学院的科研团队表示,他们已经找到证据表明HER2阳性乳腺癌复发可能是因为患者免疫反应存在由癌症引发的特异减弱。研究人员希望这一关键证据有望打开新的靶向治疗方向,甚至于有助于HER2型乳腺癌疫苗的研发。

乳腺癌复发的关键元凶:抗HER2免疫反应下降

因为HER2受体蛋白是重要的乳腺癌预后判断因子,负责肿瘤的快速扩散,所以科学家选取其抗HER2的促炎症因子(Th1)的反应作为检测参数。研究团队选取95个HER2阳性乳腺癌患者为研究对象,分离出患者体内免疫细胞用于分析Th1反应能力。

研究团队之前已经发现抗HER2的免疫机制在正常人与早期HER2患者之间存在显著差异。结果显示,相比于至少两年内未曾复发的乳腺癌患者,短期内复发的患者免疫细胞中仅仅只有1/10的抗HER2反应发生。

研究团队检测所有受试对象的免疫细胞的Th1反应后发现,抗HER2反应率最低的患者平均47个月后会出现复发可能,而抗HER2免疫反应率最高的患者平均有113个月不会复发。相关研究结果发表在《 JAMA Oncology》。

但是抗HER2免疫反应下降的原因仍然不清楚。这也是科研团队未来的研究重点。

这项最新研究预示着,未来,HER2阳性乳腺癌患者有望在治疗前、治疗中、治疗后通过血液检测监视免疫系统,从而有利于医生预测患者复发的概率,并及时干预从而降低复发概率、增强抗HER2免疫能力。

推荐阅读

Breast Cancer Recurrence Associated with Weak T Cell Response

查看更多
  • Association of Depressed Anti-HER2 T-Helper Type 1 Response With Recurrence in Patients With Completely Treated HER2-Positive Breast Cancer Role for Immune Monitoring

    Importance There is a paucity of immune signatures identifying patients with human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer (IBC) at risk for treatment failure following trastuzumab and chemotherapy. Objective To determine whether circulating anti-HER2 CD4-positive (CD4+) T-helper type 1 (Th1) immunity correlates with recurrence in patients with completely treated HER2-positive IBC. Design, Setting, and Participants Hypothesis-generating exploratory translational analysis at a tertiary care referral center of patients with completely treated HER2-positive IBC with median (interquartile range) follow-up of 44 (31) months. Anti-HER2 Th1 responses were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II–promiscuous peptides via interferon-γ (IFN-γ) enzyme-linked immunospot assay. Main Outcomes and Measures T-helper type 1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFCs]/106 cells). Anti-HER2 Th1 responses in treatment-naive patients (used as an immunologic baseline) were compared with those in patients completing trastuzumab and chemotherapy; in the latter group, analyses were stratified by recurrence status. Recurrence was defined as any locoregional or distant breast event, or both. Cox regression analysis estimated the instantaneous hazard of recurrence (ie, disease-free survival [DFS]) stratified by anti-HER2 Th1 responsivity. Results In 95 women with HER2-positive IBC (median [range] age, 49 [24-85] years; 22 treatment-naive, 73 treated with trastuzumab and chemotherapy), depressed anti-HER2 Th1 responsivity (recurrence, 2 of 25 [8%], vs nonrecurrence, 40 of 48 [83%]; P < .001), mean (SD) repertoire (0.1 [0.1] vs 1.5 [0.2]; P < .001), and mean (SD) cumulative response (14.8 [2.0] vs 80.2 [11.0] SFCs/106 cells; P < .001) were observed in patients incurring recurrence (n = 25) compared with patients without recurrence (n = 48). After controlling for confounding, anti-HER2 Th1 responsivity remained independently associated with recurrence (P < .001). This immune disparity was mediated by anti-HER2 CD4+T-bet+IFN-γ+ (Th1)—not CD4+GATA-3+IFN-γ+ (Th2) or CD4+CD25+FoxP3+ (Treg)—phenotypes, and not attributable to immune incompetence. When stratifying trastuzumab plus chemotherapy-treated patients by Th1 responsivity, Th1-nonresponsive patients demonstrated a worse DFS (median, 47 vs 113 months; P < .001) compared with Th1-responsive patients (hazard ratio, 16.9 [95% CI, 3.9-71.4]; P < .001). Conclusions and Relevance Depressed anti-HER2 Th1 response is a novel immune correlate to recurrence in patients with completely treated HER2-positive IBC. These data underscore a role for immune monitoring in patients with HER2-positive IBC to identify vulnerable populations at risk of treatment failure.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test