Abstract
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.
Highlights
Brain metastasis frequently appears in patients with lung and breast cancer as well as in melanoma patients
We found that the levels of granulocyte-monocyte colony stimulating factor (GM-CSF) in the metastatic microenvironment (MME) of the brain were upregulated as a result of these interactions
Granulocyte-monocyte colony stimulating factor (GM-CSF) is secreted from unstimulated brain endothelial cells (BEC) and from astrocytes but not from microglia (Figure 1a)
Summary
Brain metastasis frequently appears in patients with lung and breast cancer as well as in melanoma patients. Due to limited and usually non-effective treatment options, brain metastasis is associated with poor survival and constitutes an unmet clinical challenge [1,2]. Metastasis occurs relatively early in the disease and quite frequently [1]. Patients diagnosed with brain metastasis have a short overall survival [3] and systemic therapeutic options for such patients are poor and only beneficial in a limited group of patients [4]. The brain microenvironment is unique with respect to anatomy, resident cells (e.g., astrocytes, microglia), molecular milieu and the immune landscape [5,6]. The brain-invading cells in turn, contribute to the remodeling of the brain microenvironment and its establishment as a hospitable accommodation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
