The Local Cytokine and Chemokine Milieu within Malignant Effusions

Abstract

Background/Aims: 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-β₁ 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. Conclusion: 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.