Increased production of immune activation marker neopterin by colony‐stimulating factors in gynecological cancer patients

Marth, Christian; Weiss, Günter; Koza, Astrid; Reibnegger, Gilbert; Daxenbichler, Günter; Zeimet, Alain G.; Fuchs, Dietmar; Wächter, Helmut; Dapunt, O

doi:10.1002/ijc.2910580105

Cited by 7 publications

(7 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients with gynecological cancer (mostly EOC), Marth et al described an increase in urinary neopterin after treatment with hematopoietic growth factors (101) . An increase in urinary neopterin was detected both in patients treated with GM-CSF and G-CSF.…”

Section: Neopterin As Indicator Of Immune Activation Induced By Cytokmentioning

confidence: 99%

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Melichar

Solichová

Freedman

2006

Int J Gynecol Cancer

View full text Add to dashboard Cite

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.

show abstract

Section: Neopterin As Indicator Of Immune Activation Induced By Cytokmentioning

confidence: 99%

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Melichar

Solichová

Freedman

2006

Int J Gynecol Cancer

View full text Add to dashboard Cite

show abstract

“…G-CSF failed to induce IL-lra protein production in monocytes stimulated with LPS or cultured on adherent IgG (Jenkins and Arend 1993), though neopterin production by the myelomonocytic cell line THP-1 in response to IFN-7 was increased in the presence of G-CSF (Marth et al 1994). Furthermore, in contrast to the other three CSF discussed below, G-CSF did not induce any urokinase-type plasminogen activator (u-PA) activity (Hamilton et al 1991).…”

Section: A Synthesis Of Mediators and Enzymesmentioning

confidence: 99%

“…In 18 patients with acute leukemia where G-CSF was administered in the recovery phase during 27 courses of consolidation chemotherapy, peripheral blood monocytes spontaneously produced high concentrations of IL-6 ex vivo (Liu et al 1993). In 38 neutropenic gynecological cancer patients, G-CSF treatment doubled the concentration of serum neopterin (Marth et al 1994), which is regarded as a marker of macrophage activation.…”

Section: A Synthesis Of Mediators and Enzymesmentioning

confidence: 99%

“…A correlation to the expansion of the WBC was found. To investigate whether GM-CSF causes an activation of cellular immunity, urinary neopterin levels of gynecological cancer patients were assessed and found to have increased in response to GM-CSF (Marth et al 1994). Neopterin, whose physiological role is unknown, is a sensitive marker of macrophages activated by interferons (Marth et al 1994).…”

Section: T= Synthesis Of Mediators and Enzymesmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulation by colony-stimulating factors

Hartung

1999

Reviews of Physiology, Biochemistry and Pharmacology

View full text Add to dashboard Cite

“…In addition, we performed serial determinations of serum neopterin levels as a means to measure monocyte/macrophage activation since release of neopterin is a sign of macrophage activation 24,25 and administration of GM-CSF results in increased production of neopterin. 26,27 …”

Section: Introductionmentioning

confidence: 99%

Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma

S̄pitler

Cao

Piironen

et al. 2017

American Journal of Clinical Oncology

View full text Add to dashboard Cite

OBJECTIVES We investigated the development of binding and neutralizing antibodies to GM-CSF in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biologic effects. METHODS Fifty-three patients with high-risk melanoma which had been surgically excised were treated with GM-CSF, 125 µg/m2 daily for 14 days every 28 days for 1 year following surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on Study Days 155 and 351. Blood draws for testing biologic effects were keyed to GM-CSF administration: Days 0 (before), 15 (after 14 days on GM-CSF), 29 (after 14 days off GM-CSF), 155, and 351 (after 14 days on GM-CSF in the 6th and 13th cycle of treatment). RESULTS Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell (WBC) count, percent eosinophils, or neopterin levels engendered by GM-CSF administration, was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies. CONCLUSIONS Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biologic effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials.

show abstract

Increased production of immune activation marker neopterin by colony‐stimulating factors in gynecological cancer patients

Cited by 7 publications

References 12 publications

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Immunomodulation by colony-stimulating factors

Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma

Contact Info

Product

Resources

About