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Fig. 3 | Journal of Experimental & Clinical Cancer Research

Fig. 3

From: Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

Fig. 3

Proposed mechanisms for the reconfiguration of tumor-associated macrophages under immune checkpoint blockade. Both CTLA-4 and PD-1 blockade have shown to be capable of inducing a profound remodeling of the myeloid cell compartment in the tumor and in the periphery, reconfiguring its immunosuppressive function into a pro-inflammatory one. This effect has been suggested to be mediated indirectly, via the reinvigoration of T cells and the INF-gamma cytokine secretion allowing for the pro-inflammatory polarization of monocytes newly infiltrating the tumor. A direct cis-action of anti-PD-1 and anti-CTLA-4 on tumor-associated macrophages expressing these receptors, resulting in part in reduced arginase-1 expression, is also proposed. This reconfiguration of the intratumoral myeloid compartment may in turn contribute to enhance the T cell response directed against the tumor notably through the capacity of tumor-associated macrophages to act as potent antigen-presenting cells. PD-1 blockade was also shown to impact on the myeloid cell lineage maturation process, allowing myeloid precursor cells to pursue their maturation into terminal effector macrophages, thereby overcoming the block in maturation leading to the generation of MDSCs observed in cancer-associated emergency myelopoiesis

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