Metinel node--the first lymph node draining a metastasis--contains tumor-reactive lymphocytes.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dahl
Kjell
K
Department of Surgery, Stockholm South General Hospital, Stockholm, 118 83, Sweden. kjell.dahl@sodersjukhuset.se
Karlsson
Mona
M
Marits
Per
P
Hoffstedt
Anna
A
Winqvist
Ola
O
Thörn
Magnus
M
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary*; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control; D011300:Preoperative Care; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012394:Rosaniline Dyes; D013671:Technetium Tc 99m Sulfur Colloid
D019275:Radiopharmaceuticals; D012394:Rosaniline Dyes; D013671:Technetium Tc 99m Sulfur Colloid; D007371:Interferon-gamma; C008769:sulfan blue