Abstract
Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.
Highlights
Tumor-associated macrophages (TAMs) are key players in cancers influencing progression, metastasis and tumor recurrence
And functionally similar to trabectidin, lurbinectedin has shown promising clinical results in the treatment of small cell lung cancer, alone or in combination with checkpoint inhibitors or conventional chemotherapeutics [23,24]. Another class of drugs that showed secondary efficacy in depleting TAMs when used in chemotherapeutic regimens, are efficacious alone or in combination with other chemotherapeutics in various tumor models, even if drug removal elicited the recruitment of new macrophages and the rapid development of metastases in breast cancer [39]
The activated downstream signaling pathways converge on the PI3K/Akt axis that is involved in TAM activation and polarization towards the M2 phenotype, associated with the promotion of efferocytosis, which limits the inflammatory response, fostering the production of immunosuppressive cytokines and preventing the immune cell activation in response to cancer cell death in solid tumors
Summary
TAMs are key players in cancers influencing progression, metastasis and tumor recurrence. M1 macrophages secrete proinflammatory cytokines and express markers typically used to identify the M1 phenotype [10]. M1 secrete anti-inflammatory cytokines, TGFβ and express M2 phenotype markers (Figure 1). M1 macrophages secrete proinflammatory cytokines and resistin-like molecule α (FIZZ1), macrophage mannose receptor (MMR). The alternatively activated macrophages (M2) are involved in the resolution of inflammation and suppress the immunity against parasites and tumor cells, enabling the tumor microenvironment to promote cancer progression and metastasis. M2 TAMs secrete anti-inflammatory cytokines, TGFβ and express M2 phenotype markers (Figure 1). The M2 profile is characterized by upregulation of genes such as arginase 1 (Arg1), resistin-like molecule α (FIZZ1), macrophage mannose receptor (MMR) 1, (Mrc1) and chitinase-like protein Ym1 [10]
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
