Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration.
BACKGROUND
Interleukin-2 (IL-2) has direct pluripotent effects on cells with immune and inflammatory function. Which of these effects has a critical role in mediating tumor regression remains enigmatic. In this study, we compared early changes in transcriptional profiles of circulating mononuclear cells with those occurring within the microenvironment of melanoma metastases following systemic IL-2 administration.


RESULTS
The results suggest that the immediate effects of IL-2 administration on the tumor microenvironment is transcriptional activation of genes predominantly associated with monocyte cell function; minimal effects were noted on migration, activation and proliferation of T cells. However, production of chemokines and markers of adhesion and migration within few hours of IL-2 administration may be responsible for a secondary recruitment of immune cells to the tumor site later.


CONCLUSIONS
Our results suggest that IL-2 induces inflammation at tumor sites with three predominant secondary effects: activation of antigen-presenting monocytes; massive production of chemoattractants that may recruit other immune cells to the tumor (including MIG and PARC, which are specific for T cells); and activation of cytolytic mechanisms in monocytes (calgranulin, grancalcin) and NK cells (NKG5, NK4).
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Monica C
MC
Panelli
Ena
E
Wang
Giao
G
Phan
Markus
M
Puhlmann
Lance
L
Miller
Galen A
GA
Ohnmacht
Harvey G
HG
Klein
Francesco M
FM
Marincola
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008954:Models, Biological; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
D000970:Antineoplastic Agents; D007376:Interleukin-2; D012333:RNA, Messenger