Inter-Tumor Heterogeneity-Melanomas Respond Differently to GM-CSF-Mediated Activation.
Adi MosheSivan IzraelyOrit Sagi-AssifSapir MalkaShlomit Ben-MenachemTsipi MeshelMetsada Pasmanik-ChorDave S B HoonIsaac P WitzPublished in: Cells (2020)
Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. Whereas cells of one melanoma acquired pro metastatic features following exposure to GM-CSF, cells from another melanoma either did not respond or became less malignant. We propose that inter-melanoma heterogeneity as manifested by differential responses of melanoma cells (and perhaps also of other tumor) to GM-CSF may be developed into a predictive marker providing a tool to segregate melanoma patients who will benefit from GM-CSF therapy from those who will not.
Keyphrases
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- cerebrospinal fluid
- squamous cell carcinoma
- endothelial cells
- small cell lung cancer
- peritoneal dialysis
- prognostic factors
- early stage
- stem cells
- patient reported outcomes
- oxidative stress
- cell cycle arrest
- smoking cessation
- replacement therapy
- recombinant human