Abstract
MAFB is a transcription factor specifically expressed in macrophages. Using in vitro and in vivo in mouse tumor models, our previous study suggested that MAFB could be a suitable marker for tumor-associated macrophages (TAMs), besides MAFB is expressed in anti-inflammatory alternatively activated M2 macrophages in vitro. TAMs play a key role in the tumor microenvironment (TME) by inducing immunosuppression, angiogenesis, tumor invasion, and metastasis. However, finding a suitable specific biomarker and target for TAMs is challenging. Here, we demonstrated that MAFB could be used as a biomarker for TAMs and consequently, for severity in various human cancers, including lung, liver, colon, and pancreatic cancers, according to the immunohistochemical analysis of the expression of MAFB, CD68, and CD204.
Moreover, In a cohort of lung adenocarcinomas patients (n = 120), increased MAFB expression was related to increased tendency towards metastasis and poor overall survival rate. Further, we showed that MAFB expression was positively correlated to the expression of CD204 and CD68 in both human hepatocarcinoma and colon cancers. Our findings indicate that MAFB as a specific biomarker can be used as prognostic marker for Metastasis potential in Lung adenocarcinomas patients and also a biomarker for the severe Liver, Colon and pancreatic cancers. In addition, we showed that MAFB was expressed in Tumor associated macrophages expressing Programmed cell death protein-1 and/or Programmed cell death ligand 1 (TAM PD-1+ and TAM PD-L1+) cells in both human lung adenocarcinomas and Lewis lung carcinoma (LLC) mouse model. These findings indicate that MAFB can be a potential target for drug development against TAM PD-1+ and TAM PD-L1+ cells. In summary, transcriptional factor MAFB can be used as a specific biomarker, prognostic marker and a potential target for cancer immunotherapy against TAMs.
Targeting CAMKII to reprogram tumor-associated macrophages and inhibit tumor cells for cancer immunotherapy with an injectable hybrid peptide hydrogel
