Abstract
In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.
Highlights
Macrophages are specialized phagocytic cells of the innate immune system
Presence of tumor-associated macrophages (TAMs) in Different Tumor Types Taking into account the properties of macrophages described in the previous paragraph, it is commonly accepted that high numbers of TAMs with an M2-like anti-inflammatory phenotype are typically associated with poor patient outcome, while TAMs polarization towards an M1-like pro-inflammatory phenotype tend to correlate with favorable prognosis and longer survival (Table 1) [59,60,61,62,63]
Cornellisen et al demonstrated that the CD163+ macrophages/total TAM ratio could be used as a prognostic marker of local tumor outgrowth (LTO), a common complication in Malignant Pleural Mesothelioma (MPM) after invasive procedure
Summary
Macrophages are specialized phagocytic cells of the innate immune system. They belong to the mononuclear phagocyte system, comprising both tissue resident macrophages and circulating monocytes, which are available to be recruited at sites of inflammation and tissue damage, such as tumors. Differentiating monocytes, reaching the tissues, can meet and adapt to particular local stimuli able to activate distinct genetic programs [1,2,3,4,5] In this broad spectrum of activation states, two polarized extremes have been defined: the M1 (or classically activated, pro-inflammatory/anti-tumoral) macrophages and the M2 (or alternatively activated, anti-inflammatory/pro-tumoral). M1-like macrophages are able to neutralize bacterial infections and produce pro-inflammatory cytokines (e.g., IL-1β, TNF-α, and IL-12) They are able to kill cancer cells, inhibit angiogenesis, and promote adaptive immune responses. TAMs are macrophages, which have been shaped by tumor-derived factors to promote cancer progression These corrupted cells are responsible for progression and resistant to conventional antitumor treatments, such as chemotherapy or radiotherapy, and to the latest immunotherapies, such as anti-PD1 [3,6,7,8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
