Abstract 1694: Systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increases T cell receptor diversity in localized and metastatic prostate cancer patients

2017 ◽  
Author(s):  
David Y. Oh ◽  
Li Zhang ◽  
Jason Cham ◽  
Alan Paciorek ◽  
Mark Klinger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
T Cell Receptor ◽  
Metastatic Prostate Cancer ◽  
Cell Receptor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 713-723
Author(s):  
AM Stewart-Akers ◽  
JS Cairns ◽  
DJ Tweardy ◽  
SA McCarthy
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Thymocyte Proliferation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.

scholarly journals Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 713-723 ◽  
Author(s):  
AM Stewart-Akers ◽  
JS Cairns ◽  
DJ Tweardy ◽  
SA McCarthy
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Thymocyte Proliferation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 1167-1173 ◽  
Author(s):  
N J Meropol ◽  
D E Wood ◽  
J Nemunaitis ◽  
N J Petrelli ◽  
B J Lipman ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Infection Prophylaxis ◽  
Colony Stimulating Factor ◽  
Postoperative Infections ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
To Receive ◽  
Stimulating Factor

PURPOSE Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Randomized Trial of Influenza Vaccine With Granulocyte-Macrophage Colony-Stimulating Factor or Placebo in Cancer Patients

2002 ◽  
Vol 20 (21) ◽  
pp. 4313-4318 ◽  
Author(s):  
Ramesh K. Ramanathan ◽  
Douglas M. Potter ◽  
Chandra P. Belani ◽  
Samuel A. Jacobs ◽  
Stefan Gravenstein ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Cancer Patients ◽  
Controlled Trial ◽  
Fold Increase ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Trivalent Influenza Vaccine ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would improve response to influenza vaccination in cancer patients. PATIENTS AND METHODS: In a randomized, patient-blinded, placebo-controlled trial carried out in 1997 to 2000, 133 patients were stratified into five groups of treatment and disease. Single doses of standard split trivalent influenza vaccine and either placebo or 250 μg of GM-CSF were administered at the same time. Hemagglutination inhibition assay titers were measured before and 4 weeks after vaccination. RESULTS: Standard analyses, which define response as at least a four-fold increase in titers, detect no effect of GM-CSF for any of the three influenza subtypes in the trivalent vaccines (P ≥ .12). Analysis that includes the magnitude of the change in titers and combines responses of the subtypes suggests that the placebo group had the greater response (P = .051), thus indicating that GM-CSF does not improve response. Ancillary analyses show that response declines both with increasing age and with higher initial titers. The fraction of patients with at least a four-fold increase in titers was 0.36 (95% confidence interval, 0.29 to 0.42) CONCLUSION: A single 250-μg dose of GM-CSF administered with the influenza vaccine does not improve response to vaccination. Response in cancer patients is low and declines as age and initial titer increase.

Prostate-Specific Antigen Kinetics as a Measure of the Biologic Effect of Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Serologic Progression of Prostate Cancer

2003 ◽  
Vol 21 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Brian I. Rini ◽  
Vivian Weinberg ◽  
Robert Bok ◽  
Eric J. Small
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Specific Antigen ◽  
Local Therapy ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Biologic Effect ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Purpose: To determine the biologic effect of granulocyte-macrophage colony-stimulating factor (sangramostim, GM-CSF; Immunex Corporation, Seattle, WA) as measured by prostate-specific antigen (PSA) kinetics in patients with serologic progression of prostate cancer after definitive local therapy. Patients and Methods: Patients with prostate cancer who had undergone previous definitive surgical or radiation therapy with nonmetastatic, recurrent disease as manifested by a rising PSA between 0.4 ng/mL and 6.0 ng/mL were enrolled on this phase II trial. Patients received 250 μg/m2/day of subcutaneous GM-CSF on days 1 through 14 of a 28-day cycle. PSA was measured at day 1 of each cycle. Results: Thirty patients with serologic progression of prostate cancer were treated. The median pretreatment PSA was 2.9 ng/mL. Of the 29 evaluable patients, three patients (10%; 95% confidence interval, 2% to 27%) achieved a 50% reduction in PSA. For the patients (n = 26) in whom the on-treatment PSA doubling time could be calculated, the median PSA doubling time increased from 8.4 months to 15 months (P = .001), and the median slope of the PSA versus time curve decreased with treatment (P = .004). Therapy was well tolerated by all patients, with an average treatment duration of 16.5 cycles (range, 5 to 33). Conclusion: GM-CSF has a biologic effect in patients with serologic progression of prostate cancer after definitive local therapy, as measured by PSA declines and modulation of PSA kinetics.

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