HER2阳性乳腺癌患者在接受治疗后出现复发可能是由于身体免疫系统存在一种癌症造成的特异性缺陷所导致，而根据宾夕法尼亚大学Perelman医学院研究人员的一项最新研究成果，靶向HER2的疫苗能够对这种免疫系统缺陷进行补救。相关研究结果发表在国际学术期刊JAMA Oncology上。
研究结果显示乳腺癌复发病人体内的T细胞与未复发病人体内的T细胞相比，其对HER2受体蛋白的应答要弱得多，这表明在未来HER2阳性乳腺癌病人或可在治疗前，治疗过程中以及治疗后检测免疫系统应答情况预测复发风险，通过促进靶向HER2的免疫治疗方法降低乳腺癌复发风险。
该研究团队一直致力于研究免疫系统在乳腺癌病人中的作用，开发潜在的癌症疫苗。在这项最新研究中，研究人员从95名患有侵袭性HER2阳性乳腺癌的女性体内分离得到免疫细胞，分析了这些细胞对HER2生长因子受体蛋白产生Th1免疫应答的能力。HER2阳性乳腺癌细胞能够过表达HER2受体帮助细胞进行快速增殖。
他们发现从出现乳腺癌复发的女性体内分离得到的免疫细胞与未复发乳腺癌患者体内的免疫细胞相比，它们抗HER2应答能力仅是后者的十分之一。对所有病人的抗HER2应答情况进行分析，研究人员发现应答能力最弱的患者仅在治疗后平均维持了47个月的无疾病状态，而应答能力最强的患者平均维持了113个月。
研究人员表示，它们检测之后发现复发病人体内的免疫系统并不存在其他缺陷，仅在抗HER2应答方面存在缺陷，并且利用疫苗可以重建免疫系统对HER2的特异性应答。
目前，关于病人如何在HER2阳性肿瘤形成发展过程中丧失抗HER2免疫应答反应仍不清楚，如果能够了解其中的机制将对HER2阳性乳腺癌治疗方法的开发，防止癌症复发具有重要意义。
doi:10.1001/jamaoncol.2015.5482
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
Jashodeep Datta, MD1; Megan Fracol, MD1; Matthew T. McMillan, BA1; Erik Berk, PhD1; Shuwen Xu, MD1; Noah Goodman, MPH2; David A. Lewis, BA2; Angela DeMichele, MD, MSCE2,3; Brian J. Czerniecki, MD, PhD1,4
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.