This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Negin, B. Articles by Atkins, M. PubMed PubMed Citation Articles by Negin, B. Articles by Atkins, M.

Effect of Melanoma on Immune Function in the Regional Lymph Node Basin

Authors' Affiliation: Cutaneous Oncology Program, Beth Israel Deaconess Medical Center, and Project 5 and the Immune Monitoring and Biostatistics Cores of the Harvard Skin Cancer Specialized Programs of Research Excellence, Boston, Massachusetts

Requests for reprints: Michael B. Atkins, Beth Israel Deaconess Medical Center, Room 412, MASCO Building, 375 Longwood Avenue, Boston, MA 02215. Phone: 617-632-9250; Fax: 617-632-9260; E-mail: MAtkins{at}bidmc.harvard.edu.

Purpose: To determine if melanoma within the tumor microenvironment will result in immunosuppression within the draining lymph node as measured by down-regulation of T-cell receptor (TCR ) expression.

Experimental Design: Patients with clinical stage I to III melanoma undergoing wide local excision and sentinel lymph node biopsy or therapeutic lymph node dissection were consented to have a portion of their lymph node sampled. Lymph nodes were classified as macroscopically involved (TI), microscopically involved (MI), noninvolved with positive wide excision (NI+), or noninvolved with negative wide excision (NI–). Lymphocytes were stained using antibodies to TCR and other immune cells and analyzed via flow cytometer. Reverse transcription-PCR was used to assess for mediators of immunosuppression.

Results: Fifty patient lymph node samples (15 TI, 7 MI, 9 NI+, and 19 NI–) were evaluated. Increasing involvement of tumor in the lymph node was associated with decreasing TCR chain expression (TI 56%, MI 76%, and NI– 89%). Differences between TI and MI (P = 0.005), TI and NI– (P = 0.0001), and MI and NI– (P = 0.019) were statistically significant. There was also a significant difference between TCR chain expression of NI+ and NI– (73% versus 89%; P = 0.0016). A trend toward increased arginase expression in tumor-involved lymph nodes was detected by reverse transcription-PCR.

Conclusions: Melanoma involvement of regional nodes is associated with loss of TCR expression that is inversely related to tumor burden. Residual melanoma within the wide local excision specimen is associated with TCR loss in noninvolved sentinel lymph nodes, suggesting that immune modulation precedes tumor spread.