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.
We studied several in vitro activities of tumor-associated lympho-monocytes (TALMs) and the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)alpha, interferon (IFN)gamma and soluble IL-2 receptor (slL-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-1alpha, IL-1beta and TNF alpha 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 IFN gamma amounts (only from pleural effusions) were significantly higher. IL-1alpha, IL-1beta, IL-2, IL-6 and TNF alpha production from patient PBMCs was lower than that of control PBMCs, whereas production of IL-4, IL-10 and IFN gamma was higher than that of control PBMCs. Both in peritoneal and in pleural effusions concentrations of IL-1alpha, IL-1beta and IL-4 were not different from those measured in autologous serum, whereas those of IL-6, IL-10, TNF alpha, IFN gamma 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-1alpha, IL-1beta, IL-2, IL-6, TNF alpha and sIL-2R were higher in patient than in control sera, whereas those of IL-4, IL-10 and IFN gamma 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.
Mantovani
G
G
Department of Medical Oncology, University of Cagliari, Italy. Mantovan@pacs.unica.it
Macciò
A
A
Pisano
M
M
Versace
R
R
Lai
P
P
Esu
S
S
Massa
E
E
Ghiani
M
M
Dessì
D
D
Melis
G B
GB
Del Giacco
G S
GS
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001202:Ascitic Fluid / Q000473:pathology*; D017252:CD3 Complex / Q000276:immunology; D002453:Cell Cycle; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010996:Pleural Effusion / Q000473:pathology*; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011994:Recombinant Proteins