Mother knows best: Lessons from fetomaternal tolerance applied to cancer immunity

Failure of the immune system to recognize and eradicate tumor cells has deadly consequences. It is possible that the normal host response to the inflammatory environment created by many cancers - the body's natural attempt at wound repair and restoration of tissue integrity - is one of counter-regulation that paradoxically favors tumor growth. A physiologic condition where this situation is favorable (and even required) is that of normal pregnancy, where blastocyst implantation creates endometrial inflammation, and the maternal response in turn supports angiogenesis and tolerance required for placentation. Lack of such inflammation and resultant maternal immunologic engagement can lead to serious pregnancy complications including fetal loss, highlighting how important the fetomaternal immunologic dialogue is for survival. Here, we describe how the dynamics of fetomaternal tolerance can help disentangle complex cancer/host immunologic interactions and provide new avenues for immunologic reconstitution in patients with cancer.