Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcγRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor α (TNF-α) during mixed culture of monocytes with LeY+SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-α release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcγR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcγRI. In contrast, mAb-induced TNF-α release mainly depended on the activation of monocyte FcγRII. Neutralization of TNF-α showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-α release which seemed to be triggered by activation of different types of FcγR. © 2000 Cancer Research Campaig

High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer

The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300–0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC

Effects of Prostaglandin E1 analogue, Misoprostol, on the development of adjuvant arthritis in rats

Prostaglandins (PG) E , E and the PGE analogue, misoprostol, have been shown to inhibit T-cell functions and the production by activated monocytes or macrophages of interleukin-1, indicating that these PGs may have potential anti-arthritic activity by suppressing T-cell and monocyte activity. In view of this the potential anti-arthritic effects of the long half-life PG, misoprostol (MPL), were examined in adjuvant arthritic rats under prophylactic and therapeutic treatment regimes. Transcutaneous or subcutaneous MPL given at 200 Μg/kg/day but not at 50 or 5 Μg/kg/day when given 0 to +5 or 0 to + 14 days post-induction inhibited the development of the disease whereas the orally administered drug was without effects. MPL given transcutaneously with oral indomethacin (1 or 2 mg/kg/day) on days +17 to + 30 post-induction produced greater anti-inflammatory effects than with this NSAID alone. MPL given orally in combination with this NSAID did not enhance the anti-inflammatory effects of the latter. MPL 200 Μg/kg given transcutaneously exhibited anti-ulcer activity against indomethacin (30 mg/kg p.o.), naproxen (10 mg/kg i.p.) or piroxicam (5 mg/kg i.p.) induced gastric damage in arthritic rats and this was comparable with that from 100 Μg/kg MPL given orally. These results show that MPL has both unique anti-arthritic effects only when given transcutaneously or parenterally as well as anti-ulcer activity.K. D. Rainsford, M. W. Whitehouse and B. Vernon-Robert