Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Hematol Oncol. 2010 Sep 9;3:30. doi: 10.1186/1756-8722-3-30.
Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor.Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression. Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy. Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects.This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy.
套细胞淋巴瘤（MCL）是一种罕见且侵袭性较强的 B 细胞非霍奇金淋巴瘤。患者对常规化疗逐渐产生耐药性，预后较差。然而，最近有报道称，使用 mTOR 抑制剂替西罗莫司治疗难治性 MCL 的缓解率为 38%。在这里，我们有机会研究了一例难治性 MCL 患者，该患者在接受替西罗莫司治疗两个月后肿瘤消退，无进展生存期为 10 个月。在该病例中，在替西罗莫司治疗前和治疗后六个月分别进行了淋巴结活检。比较两次活检结果显示，替西罗莫司通过细胞周期阻滞抑制肿瘤细胞增殖，但未诱导凋亡肿瘤细胞数量发生任何变化。除了这种细胞抑制作用外，替西罗莫司还具有抗血管生成作用，可降低肿瘤微血管密度和 VEGF 表达。此外，在接受替西罗莫司治疗 6 个月后，还发现了许多片状、界限分明的纤维化区域，与坏死组织修复后相符。因此，替西罗莫司通过相关的细胞抑制和抗血管生成作用降低了肿瘤负担。这种替西罗莫司对肿瘤组织的双重作用可能有助于解释其最近在难治性 MCL 中的疗效，这些患者对常规化疗耐药。
