GM-CSF; brain metastasis; melanoma; metastatic microenvironment; genomics
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.
Moshe, Adi; Izraely, Sivan; Sagi-Assif, Orit; Malka, Sapir; Ben-Menachem, Shlomit; Meshel, Tsipi; Pasmanik-Chor, Metsada; Hoon, Dave; and Witz, Isaac P, "Inter-Tumor Heterogeneity-Melanomas Respond Differently to GM-CSF-Mediated Activation." (2020). Articles, Abstracts, and Reports. 3421.