Good CARMA: Turning bad tumor-resident myeloid cells good with chimeric antigen receptor macrophages

In religious philosophy, the concept of karma represents the effect of one's past and present actions on one's future. Macrophages are highly plastic cells with myriad roles in health and disease. In the setting of cancer, macrophages are among the most plentiful members of the immune microenvironment where they generally support tumor growth and restrain antitumor immunity. However, macrophages are not necessarily born bad. Macrophages or their immediate progenitors, monocytes, are induced to traffic to the tumor microenvironment (TME) and during this process they are polarized toward a tumor-promoting phenotype. Efforts to deplete or repolarize tumor-associated macrophages (TAM) for therapeutic benefit in cancer have to date disappointed. By contrast, genetic engineering of macrophages followed by their transit into the TME may allow these impressionable cells to mend their ways. In this review, we summarize and discuss recent advances in the genetic engineering of macrophages for the treatment of cancer.

Automated summary

In religious philosophy, karma represents the long-term impact of past and present actions. Macrophages, versatile cells in health and disease, play a significant role in cancer. They typically support tumor growth and suppress anti-tumor immunity. Efforts to modify the behavior of tumor-associated macrophages (TAM) for therapeutic purposes have not yet been successful. However, genetic engineering of macrophages shows promise in redirecting their functions for the treatment of cancer.