Figure 2.

Myeloid-linked mechanisms by which polyamines promote immunosuppression in cancer. While the mechanisms are still being uncovered, there are several potential mechanisms for why polyamine accumulation in myeloid cells is immunosuppressive (A). One hypothesis is that the propensity of alternatively activated macrophages to consume arginine, the precursor to polyamines, deplete arginine from the inflammatory microenvironment sequestering it from T-cells that need it for activation/function (B). Another proposed mechanism is that polyamine generation by myeloid cells directly feeds tumors as they actively take-up polyamines (C). Another mechanistic study indicated that polyamines drive mitochondrial gene expression and promote the metabolic phenotype associated with alternatively activated macrophages (D). We have recently shown that polyamine can be used as a mechanism to buffer intracellular pH to allow for the survival and function of myeloid cells in brain tumors (E). Despite the growing list of mechanisms by which polyamines promote immune suppression in myeloid cells, much of the biology is still yet to be determined. Figure created with BioRender.com.