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

Dahl K, Karlsson M, Marits P, Hoffstedt A, Winqvist O, Thörn M - Ann. Surg. Oncol. (2008)

Bottom Line: 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.In six patients, a preoperative lymphoscintigraphy was performed.Eight of the nineteen patients received immunotherapy on the basis of tumor-reactive T cells derived from the metinel nodes.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Stockholm South General Hospital, Stockholm, 118 83, Sweden. kjell.dahl@sodersjukhuset.se

ABSTRACT

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.

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Related in: MedlinePlus

Amount of interferon gamma secreted into the supernatant measured by enzyme-linked immunosorbent assay. Data presented are for patient 7 after 35 days of in vitro cell culture.
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Fig3: Amount of interferon gamma secreted into the supernatant measured by enzyme-linked immunosorbent assay. Data presented are for patient 7 after 35 days of in vitro cell culture.

Mentions: Cells from patient 8, stimulated at the end of the expansion, demonstrated a high production of IFN-γ of >1000 pg/mL (Fig. 3) and no detectable IL-4 (data not shown), indicating a Th1 response. In an additional patient (patient 5), the stimulated IFN-γ secretion was 155 pg/mL while only a low IL-4 production of 30 pg/mL was found, again demonstrating a Th1-predominant response pattern.Fig. 3.


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

Dahl K, Karlsson M, Marits P, Hoffstedt A, Winqvist O, Thörn M - Ann. Surg. Oncol. (2008)

Amount of interferon gamma secreted into the supernatant measured by enzyme-linked immunosorbent assay. Data presented are for patient 7 after 35 days of in vitro cell culture.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2277445&req=5

Fig3: Amount of interferon gamma secreted into the supernatant measured by enzyme-linked immunosorbent assay. Data presented are for patient 7 after 35 days of in vitro cell culture.
Mentions: Cells from patient 8, stimulated at the end of the expansion, demonstrated a high production of IFN-γ of >1000 pg/mL (Fig. 3) and no detectable IL-4 (data not shown), indicating a Th1 response. In an additional patient (patient 5), the stimulated IFN-γ secretion was 155 pg/mL while only a low IL-4 production of 30 pg/mL was found, again demonstrating a Th1-predominant response pattern.Fig. 3.

Bottom Line: 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.In six patients, a preoperative lymphoscintigraphy was performed.Eight of the nineteen patients received immunotherapy on the basis of tumor-reactive T cells derived from the metinel nodes.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Stockholm South General Hospital, Stockholm, 118 83, Sweden. kjell.dahl@sodersjukhuset.se

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus