Tumor-associated lympho-monocytes from neoplastic effusions are immunologically defective in comparison with patient autologous PBMCs but are capable of releasing high amounts of various cytokines

Abstract

We studied several in vitro activities of tumor-associated lympho-monocytes (TALMs) and the concentrations of interleukin (IL)-1α, IL-1β, 1L-2, 1L-4, IL-6, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ and soluble IL-2 receptor (sIL-2R) in neoplastic effusions and in the serum of advanced stage cancer patients. Comparisons were made with autologous peripheral blood mononuclear cells (PBMCs). Autologous PBMCs were compared with PBMCs from normal subjects used as controls. TALMs were collected from 13 peritoneal and 18 pleural neoplastic effusions, secondary to primary tumors of different sites. After PHA stimulation, concentrations of IL-1α, IL-1β and TNFα in culture media of TALMs both from peritoneal and pleural effusions were lower than those of autologous PBMCs and, similarly, concentrations of IL-4 and IL-10 in culture media of TALMs from peritoneal effusions were lower than those of autologous PBMCs, whereas concentrations of IL-4 and IL-10 in culture media of TALMs from pleural effusions were in the same range as those of autologous PBMCs. On the contrary, IL-2, IL-6 and IFNγ amounts (only from pleural effusions) were significantly higher. IL-1α, IL-1β, IL-2, IL-6 and TNFα production from patient PBMCs was lower than that of control PBMCs, whereas production of 1L-4, IL-10 and IFNγ was higher than that of control PBMCs. Both in peritoneal and in pleural effusions concentrations of IL-1α, IL-1β and IL-4 were not different from those measured in autologous serum, whereas those of IL-6, IL-10, TNFα, IFNγ and sIL-2R were significantly higher. The amounts of IL-2 in pleural effusions were not different from those of autologous serum, but in peritoneal effusions they were higher than those of autologous serum. The amounts of IL-1α, IL-1β, IL-2, IL-6, TNFα and sIL-2R were higher in patient than in control sera, whereas those of 1L-4, IL-10 and IFNγ were in the same range in patient and in control sera. Cell cycle analysis of cultured TALMs and PBMCs (from 3 patients) showed a significant accumulation of TALMs in the non-cycling G0/G1 cell population compared with autologous PBMCs.