Dahl Kjell, Karlsson Mona, Marits Per, Hoffstedt Anna, Winqvist Ola, Thörn Magnus
Department of Surgery, Stockholm South General Hospital, Stockholm, 118 83, Sweden.
Ann Surg Oncol. 2008 May;15(5):1454-63. doi: 10.1245/s10434-007-9788-7. Epub 2008 Feb 26.
We previously identified tumor-reactive lymphocytes in the first lymph nodes that drain the primary tumor. In this study, we performed lymphatic mapping to investigate the possibility of finding the first lymph nodes that drain metastases, and of learning whether these lymph nodes contained tumor-reactive lymphocytes suitable for adoptive immunotherapy.
Nineteen patients were studied. The primary tumor site was colorectal cancer in seven patients, malignant melanoma in four, ovarian cancer and breast cancer in two, and one each with pancreatic cancer, cholangiocarcinoma, leiomyosarcoma, and squamous cellular cancer of the tongue. By injection of Patent blue dye or radioactive tracers around the metastases, we identified draining lymph nodes from liver metastases (n = 9), intra-abdominal local recurrences (n = 3), and regional lymph node metastases (n = 7). In six patients, a preoperative lymphoscintigraphy was performed.
We located the first draining lymph node or nodes from metastases or local recurrences; we named them "metinel nodes." Lymphocytes from the metinel nodes proliferated, showed clonal expansion, and produced interferon gamma (via in vitro expansions on stimulation with tumor homogenate) and interleukins, all of which demonstrate the characteristics of tumor-reactive lymphocytes. Eight of the nineteen patients received immunotherapy on the basis of tumor-reactive T cells derived from the metinel nodes.
We demonstrate that it is possible to locate the first lymph nodes draining subcutaneous, lymphatic, and visceral metastases, the so-called metinel nodes. Metinel node-derived lymphocytes may be used to treat disseminated solid cancer, and clinical trials should evaluate the effect of such treatment.
我们之前在引流原发性肿瘤的第一组淋巴结中发现了肿瘤反应性淋巴细胞。在本研究中，我们进行了淋巴绘图，以探究找到引流转移灶的第一组淋巴结以及了解这些淋巴结是否含有适合过继性免疫治疗的肿瘤反应性淋巴细胞的可能性。
对19名患者进行了研究。原发性肿瘤部位为7例结直肠癌、4例恶性黑色素瘤、2例卵巢癌和乳腺癌，另有1例分别为胰腺癌、胆管癌、平滑肌肉瘤和舌鳞状细胞癌。通过在转移灶周围注射专利蓝染料或放射性示踪剂，我们确定了来自肝转移灶（n = 9）、腹腔内局部复发灶（n = 3）和区域淋巴结转移灶（n = 7）的引流淋巴结。6例患者进行了术前淋巴闪烁显像。
我们定位到了转移灶或局部复发灶的第一组引流淋巴结；我们将其命名为“前哨淋巴结”。前哨淋巴结中的淋巴细胞增殖、显示出克隆性扩增，并产生干扰素γ（通过用肿瘤匀浆刺激后的体外扩增）和白细胞介素，所有这些都表明了肿瘤反应性淋巴细胞的特征。19例患者中有8例基于从前哨淋巴结获得的肿瘤反应性T细胞接受了免疫治疗。
我们证明了定位皮下、淋巴和内脏转移灶的第一组引流淋巴结即所谓的前哨淋巴结是可行的。前哨淋巴结来源的淋巴细胞可用于治疗播散性实体癌，临床试验应评估这种治疗的效果。
