The Contribution of the Immune System in Bone Metastasis Pathogenesis
Reviewer 1 Report
General comment: The review paper submitted by Gilkes et al. describes basic knowledge of immune system on cancer metastasis including the roles and functions of immune cells and focusing on bone metastasis and the cellular and molecular mechanisms which account for interactions among cancer cells, immune cells and osteoblasts and osteoclasts. The manuscript is very well written and organized as a systematic review for the role of immune cells in bone microenvironment. The review article would be useful for research and education to learn and survey the fundamental information in cancer metastasis in bone microenvironment with cancer cells, immune cells and osteoblasts/osteoclasts.
Specific comment: The authors refer to not only mechanisms of bone metastasis but also possible therapeutic strategies targeting the specific cells and/or molecules in cancer immune systems. From this point of view, this topic is timely and particularly important, because the recent Nobel Prize in physiology or medicine has been awarded for the sensational discovery of PD-1 pathway, a promising target for cancer immunotherapeutics.
Thank you for taking the time to read and comment on this review.
Reviewer 2 Report
The authors in this review focus on the role of the immune microenvironment on bone metastasis. Furthermore, they highlight the anti-tumoral and pro-tumoral function of each immune cell type and discuss of current therapeutic strategies.
This is a nice and well written review.
They are lacking of discuss the Denosumab and Galunisertib potential roles as therapeutic strategy, even if they point their targets as some of the main factors of bone metastasis.
Please see section 5 which has been added to include a discussion of Denosumab and Galunisertib as suggested by the reviewer.