DICERing macrophages for reprogramming TAMs - PubMed (original) (raw)

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DICERing macrophages for reprogramming TAMs

Mario Leonardo Squadrito et al. Cell Cycle. 2016 Dec.

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Figure 1.

Figure 1.

Suppressing DICER activity reprograms TAMs. The genetic inactivation of Dicer induces M2-like TAMs (left, light blue cell) to acquire features of M1-like TAMs (right, light green cell). This is associated with the upregulation of genes denoting a pro-inflammatory signature, including the T cell chemoattractants Cxcl9 and Cxcl10. The production of CXCL9 and 10 by the reprogrammed TAMs enhances CTL infiltration in the tumors; in turn, CTL-derived IFNγ exacerbates M1 programming of the TAMs. Restoring the expression of Let-7 in the _Dicer_-deficient TAMs using DICER-independent lentiviral vectors and a haematopoietic -cell transplantation strategy (bottom, light blue cell) attenuates the pro-inflammatory gene signature and partly rescues M2-like activation of TAMs. Conversely, blocking Let-7 activity with a LIN28A-expressing lentiviral vector (top, light green cell) prompts cultured macrophages to acquire M1-like features, including immunostimulatory properties.

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