Correlation of NK T-like CD3+CD56+ cells and CD4+CD25+(hi) regulatory T cells with VEGF and TNFalpha in ascites from advanced ovarian cancer: Association with platinum resistance and prognosis in patients receiving first-line, platinum-based chemotherapy.
BACKGROUND
Several cytokines have been associated with immune regulation and prognosis in ovarian cancer. CD4+CD25+ Tregs and CD3+CD56+ NK-like T cells are involved in the immune response against the tumor. We have investigated the association of cytokines in the ascites from patients with ovarian cancer with these populations, the platinum resistance and the prognosis of these patients.


METHODS
Ascites from 64 patients with ovarian cancer was analysed. Forty-two patients were studied at diagnosis (FIGO stage III in 40 cases) and were treated with cytoreductive surgery and platinum-based chemotherapy. Ascites from 9 patients with cirrhosis was used as control. Vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), interleukin-10 (IL10) and interleukin-12 (IL12) in ascites and serum were measured by enzyme-linked immunosorbent assay (ELISA), while lymphocytic populations were studied with three-colour flow cytometry.


RESULTS
VEGF ascites levels were inversely correlated with CD3+CD56+ cells (rho=-0.316, p=0.012), while a similar correlation was observed between TNFalpha ascites levels and CD4+CD25+(hi) cells (rho=-0.332, p=0.041). Among patients receiving first-line chemotherapy, VEGF levels <1900 pg/ml and TNFalpha levels >35 pg/ml were associated with platinum sensitivity (p=0.021 and p=0.028, respectively) and improved progression-free survival (PFS) (p=0.007 and p=0.045, respectively). Low VEGF levels were also associated with improved overall survival (p=0.026).


CONCLUSIONS
VEGF and TNFalpha ascites levels are associated with prognosis in advanced ovarian cancer. Their prognostic significance may be due to their association with immunologically important populations, namely the NK T-like CD3+CD56+ cells and the Tregs CD4+CD25+(hi) cells.
Department of Clinical Therapeutics, Medical School, University of Athens, Greece. abamias@med.uoa.gr
Aristotelis
A
Bamias
Vasiliki
V
Koutsoukou
Evangelos
E
Terpos
Marinos L
ML
Tsiatas
Christina
C
Liakos
Ourania
O
Tsitsilonis
Alexandros
A
Rodolakis
Zannis
Z
Voulgaris
G
G
Vlahos
Theocharis
T
Papageorgiou
G
G
Papatheodoridis
A
A
Archimandritis
A
A
Antsaklis
M A
MA
Dimopoulos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019002:CD56 Antigen / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D017252:CD3 Complex; D019002:CD56 Antigen; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D009944:Organoplatinum Compounds; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma