The local cytokine and chemokine milieu within malignant effusions.
OBJECTIVE
Malignant effusions offer a unique opportunity for the study of interactions between the human immune system and cancer. We have recently demonstrated that malignant effusions are characterized by an accumulation of T cells expressing chemokine receptors such as CCR4, which is commonly found on Th2 cells. In contrast, effector T cells expressing chemokine receptors typical for Th1 cells, such as CCR5, showed a diminished homing into malignant effusions.


METHODS
We analyzed concentrations of 12 different cytokines and 9 chemokines within malignant and nonmalignant effusions and investigated cytokine expression by effusion-infiltrating leukocytes.


RESULTS
We observed that concentrations of the immunoregulatory cytokine TGF-beta(1) and of angiogenic factors VEGF and IL-8 were markedly increased within effusions caused by malignancies. However, we did not observe signs of a typical Th1 or Th2 milieu. Analyzing concentrations of 9 different chemokines, we found elevated concentrations of the chemokines MDC, eotaxin, I-TAC, and MCP-1 in malignant effusions. Interestingly, tumor-infiltrating leukocytes themselves seemed to contribute strongly to the creation of a distinct cytokine/chemokine pattern within cancer-related effusions. Additional analyses suggested that this cytokine/chemokine milieu might support an enrichment of immunosuppressive leukocytes.


CONCLUSIONS
The local cytokine and chemokine milieu within malignant effusions seems to promote angiogenesis and to block an efficient immune-mediated antitumor response. An elimination of such tumor-promoting influences will be necessary in order to transform local immunotolerance into clinically relevant immune recognition of tumors causing malignant effusions.
Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. D.Atanackovic@uke.uni-hamburg.de
Djordje
D
Atanackovic
Yanran
Y
Cao
Ji-Won
JW
Kim
Stephan
S
Brandl
Ina
I
Thom
Christiane
C
Faltz
York
Y
Hildebrandt
Katrin
K
Bartels
Andreas
A
de Weerth
Susanna
S
Hegewisch-Becker
Dieter Kurt
DK
Hossfeld
Carsten
C
Bokemeyer
D051722:ADAM Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054413:Chemokine CCL11 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C111835:CCL2 protein, human; C515202:CXCL11 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054371:Chemokine CXCL11; D018925:Chemokines; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; C090222:ADAM11 protein, human