Malignancies in immune deficiencies

Abstract It is recognized that certain primary immune deficiencies are associated with increased risk of specific pathogens and this has led to a greater understanding of the role of individual genes in mediating host defense against these pathogens. In a similar fashion, the increased risk of cancers associated with primary immune deficiencies provides us with insight about immune protections from malignancies. The immune system has the ability to identify and eradicate developing cancers, a phenomenon termed “cancer immunosurveillance” (Schumacher and Schreiber, 2015). The notion of the normal immune system preventing cancer development through immune surveillance is supported by the increased risk of cancers in immunocompromized patients, including persons with AIDS (Patel et al., 2008; Shiels et al., 2010; Shiels et al., 2011; Simard et al., 2010), hematopoietic stem cell transplant recipients (Majhail, 2011; Majhail et al., 2011), and solid organ transplant recipients (Engels et al., 2011). In these secondary immune deficiencies, multiple factors can influence the risk of cancer including impaired immunosurveillance as well as therapy-related genotoxicity (Olivero et al., 2007). In contrast, patients with primary immune deficiencies provide the opportunity to more directly delineate the role of immune protection from cancer at the level of specific genes and pathways. The goals of this chapter are to review immune deficient conditions in which the occurrence of cancer is strikingly high and describe the insights we gain regarding the role of the immune system in protecting from incident cancer. We will also discuss implications for cancer screening, gaps in knowledge, and future directions in research.