[147-151] We would like to believe that in the near future TAM-targeted strategy will be clinically accepted as a valuable adjuvant therapy for Anti-infection Compound Library concentration cancer patients. However, we have come to appreciate the fact that cancer is a systemic disease and TAMs are involved in tumour progression through rather complex mechanisms. TAM-targeted therapy, therefore, requires an overall understanding about TAM functions in tumour development. One major gap in our knowledge is why TAM infiltration is associated with poor prognosis in many types of

cancers but with favourable survival in others. Although a few pieces of evidence indicate the micro-anatomical location and macrophage phenotype might be responsible for this dichotomy,[152-154] clinical evidence is substantially lacking. Second, it would be interesting to identify TAM-specific molecules

that could serve MLN8237 as targets for tumour therapy, because previous identified factors (e.g. VEGF, MMPs, TGF-β and CXCL-12) important for TAM-mediated tumour progression,[3, 4, 7-9, 75] are also produced by cancer cells themselves. Hopefully, recent clinical and experimental investigations have identified several tumour-promoting molecules (e.g. CCL-18 and IRAK-M) predominantly produced by M2 TAMs.[155, 156] Third, what should not be neglected is the close interaction between macrophages and other stromal cells within the tumour microenvironment. A better understanding of those connections will contribute to TAM-targeted adjuvant before therapies. The fourth inherent issue is how to keep the balance between ‘cancer-inhibiting inflammatory responses’ and ‘cancer-promoting inflammatory

responses’.[157, 158] More biological understandings and pharmacological approaches are needed to fill this gap of our knowledge. Furthermore, a practical issue for developing TAM-targeted therapy is that, clinically, how should a drug be administered at the right time and to the right place so that the tumour-promoting TAMs could be depleted or re-educated whereas the tumoricidal macrophages in tumours or healthy tissues remain unaffected. In summary, more comprehensive understanding of the properties of TAMs and their interactions with the tumour microenvironment, together with advances in diagnostic/therapeutic techniques, will be required to facilitate the development and clinical application of TAM-targeted adjuvant cancer therapies. Our deepest gratitude goes first and foremost to Dr Meiyi Pu for her critical reading of the manuscript and her great contribution to the English improvement. Without her help, this article could not have reached its present form. We also thank Dr Changhua Zou for her wonderful suggestion. This work was supported by a grant from the West China Hospital of Sichuan University (Huaxi Grant 13708002). The authors declare having no conflicts of interest. “
“Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine.