Phagocytosis by dendritic cells rather than MHC IIhigh macrophages is associated with skin tumour regression.
Dendritic cells (DC) are important for the induction of anti-tumour immunity and are currently being used in clinical trials. Whether DC in tumours behave the same as DC in normal tissues or whether the tumours subvert DC phenotype and function remains unknown. To address this, we have used a unique animal tumour model to compare the DC infiltrating regressing tumours with the DC infiltrating progressing skin tumours. Compared to progressor tumours, the regressor tumours were infiltrated by greater numbers of DC that were also less mature, based on MHC II expression. Apart from this, the phenotype of DC in both tumours was similar. However, compared to various control DC, they could not be classed as either mature or immature. Similar to terminally maturated DC but in contrast to fresh DC, tumour-derived DC did not express CCR5 or CXCR4, suggesting that they most closely resembled terminally matured DC. Macrophages that expressed high MHC II levels were found infiltrating progressor but not regressor tumours and in vivo were the major phagocytic cell. In contrast, DC were found to be the major phagocytic cell in regressor tumours. The results show that immune destruction and eventual regression of skin tumours occurs if DC rather than MHC II(high) macrophages are the major phagocytic cell.
Byrne
Scott N
SN
Department of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital at the University of Sydney, Australia.
Halliday
Gary M
GM
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis; D010641:Phenotype; D019707:Receptors, Chemokine / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D019707:Receptors, Chemokine