scholarly journals CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony- stimulating factor

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2910-2917 ◽  
Author(s):  
MN Saleh ◽  
SJ Goldman ◽  
AF LoBuglio ◽  
AC Beall ◽  
H Sabio ◽  
...  
Keyword(s):  
Absolute Number ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Gastrointestinal Carcinoma ◽  
Patients With Cancer ◽  
Macrophage Colony Stimulating Factor ◽  
The Absolute ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Cd16 Antigen

The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.

Human macrophage colony-stimulating factor levels in cerebrospinal fluid

Cytokine ◽  
1993 ◽  
Vol 5 (3) ◽  
pp. 250-254 ◽  
Author(s):  
Kazuya Shimoda ◽  
Seiichi Okamura ◽  
Yumi Mizuno ◽  
Naoki Harada ◽  
Akira Kubota ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1783-1787 ◽  
Author(s):  
CS Rosenfeld ◽  
C Evans ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Conditioned Media ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Colony Stimulating Activity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L- phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment.

scholarly journals Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 907-913 ◽  
Author(s):  
J Nemunaitis ◽  
JD Meyers ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
M Mori ◽  
...  
Keyword(s):  
Phase I ◽  
Fungal Infections ◽  
Allogeneic Bone Marrow Transplantation ◽  
Marrow Transplant ◽  
Human Macrophage ◽  
Allogeneic Bone ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract A phase I dose escalation trial of recombinant human macrophage colony- stimulating factor (rhM-CSF) in combination with conventional antifungal therapy was conducted in 24 marrow transplant recipients with invasive fungal infection. Daily doses ranged from 100 to 2,000 micrograms/m2/d. Toxicity, such as constitutional symptoms, directly ascribed to rhM-CSF was not observed; however, transient, dose-related thrombocytopenia was observed. Patients who received 2,000 micrograms/m2/d of rhM-CSF had a mean reduction in platelet count of 61,000/mm3 during the rhM-CSF infusion period, which was significant when compared with patients who received lower doses of rhM-CSF (P = .008). Fourteen of the 16 patients who received rhM-CSF after undergoing allogeneic bone marrow transplantation had no change in the severity of graft-versus-host disease (GVHD) while receiving rhM-CSF. One had an increase in the severity of GVHD and one had a decrease. There were no effects on neutrophil, monocyte, or lymphocyte counts. Six patients had resolution of their infections, 12 were not evaluable for response, and six did not respond. Ten patients survived 100 days after initiation of rhM-CSF and 14 died. Further trials with rhM-CSF to assess antifungal activity are indicated.

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