Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Cancer Immunol Immunother. 2013 Jun;62(6):983-7. doi: 10.1007/s00262-013-1405-y. Epub 2013 Apr 17.
B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to enhance humoral responses following vaccination has not been evaluated. We evaluated BLyS serum levels and antigen-specific antibody titers in 8 patients undergoing therapeutic temozolomide (TMZ)-induced lymphopenia, with concomitant vaccine against a tumor-specific mutation in the epidermal growth factor receptor (EGFRvIII). Our studies demonstrate that TMZ-induced lymphopenia corresponded with spikes in serum BLyS that directly preceded the induction of anti-EGFRvIII antigen-specific antibody titers, in some cases as high as 1:2,000,000. Our data are the first clinical observation of BLyS serum elevation and greatly enhanced humoral immune responses as a consequence of chemotherapy-induced lymphopenia. These observations should be considered for the development of future vaccination strategies in the setting of malignancy.
B 淋巴细胞刺激因子 (BLyS) 是一种细胞因子，参与滤泡 B 细胞的分化和存活以及体液反应的增强。已知淋巴细胞减少症会导致血清 BLyS 显著升高；然而，尚未评估利用这种效应增强接种疫苗后的体液反应。我们评估了 8 例接受治疗性替莫唑胺（TMZ）诱导的淋巴细胞减少症的患者的血清 BLyS 水平和针对表皮生长因子受体（EGFRvIII）的肿瘤特异性突变的抗原特异性抗体滴度。我们的研究表明，TMZ 诱导的淋巴细胞减少症与血清 BLyS 的飙升相对应，BLyS 的飙升直接在前抗 EGFRvIII 抗原特异性抗体滴度的诱导之前，在某些情况下高达 1:2000000。我们的数据是化疗诱导的淋巴细胞减少症导致 BLyS 血清升高和大大增强体液免疫反应的首次临床观察。这些观察结果应在恶性肿瘤的背景下考虑未来疫苗接种策略的发展。
