Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma.
The mechanism by which the immune system of a tumor-bearing host acquires tolerance toward tumor antigens is still elusive. Antigen-presenting cells (APCs) are critical regulators of the decision between immune response and tolerance. APCs that express the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) have been found to inhibit T-cell responses both in vitro and in vivo. We hypothesized that malignant tumors exploit this mechanism by recruiting IDO-expressing APCs to the tumor-draining lymph nodes. To test this hypothesis, archival tissues and records of 26 cases of lymph node dissection for invasive cutaneous melanoma were obtained. IDO immunohistochemistry was performed on 14 cutaneous tumors and 328 regional lymph nodes. Abnormal accumulations of IDO-positive cells with a monocytoid or plasmacytoid morphology were identified in the perisinusoidal regions of draining lymph nodes in 45% of nodes studied. Recruitment of IDO-positive cells was seen in nodes with and without malignancy. We hypothesize that these IDO-positive APCs may contribute mechanistically to acquired tolerance to tumor antigens. Immunostaining of tumor-draining lymph nodes for abnormal accumulation of IDO-expressing cells might thus constitute an adverse prognostic factor and could contribute to the decision process and the appropriate care of patients with this deadly disease.
Lee
Jeffrey R
JR
Institute of Molecular Medicine and Genetics, Augusta Veterans Affairs Medical Center, Department of Pathology, Medical College of Georgia, Augusta, Georgia, USA. JLEE@mail.mcg.edu
Dalton
Rory R
RR
Messina
Jane L
JL
Sharma
Madhav D
MD
Smith
David M
DM
Burgess
Russell E
RE
Mazzella
Fermina
F
Antonia
Scott J
SJ
Mellor
Andrew L
AL
Munn
David H
DH
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000276:immunology* / Q000556:secondary; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D014366:Tryptophan Oxygenase / Q000378:metabolism
D014408:Biomarkers, Tumor; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014366:Tryptophan Oxygenase