title: Long-term immunosuppression and malignancy in thoracic transplantation: where is the balance?
abstract: Cancers in post-transplant patients exhibit the same molecular and cellular properties as those in their non-transplanted counterparts and arise secondary to uncontrolled/sustained growth, apoptosis resistance, inhibition of tumor suppressors, immortalization of cells with invasion, and and metastasis. Disruption of DNA repair mechanisms, upregulation of angiogenic growth factors, impaired viral immunity and activated oncogenic viruses contribute to the initiation of malignancies in this population. This article extends and addresses the concerns in this area. We propose potential cancer prevention strategies and a possible 4-pronged approach to prevent and treat malignancies in the post-transplant population. Future research should define strategies for immune modulation, immune suppression and malignancy prevention, including methods for naive B-cell repopulation, memory B-cell reduction and biomarker identification and utilization for predicting tolerance. Non-immune therapies, such as adjunct preventive methods and goals to modify risk factors, may reduce incidence of malignancies and pave the way to better outcomes. The role of statins is of particular interest in this context due to their pleiotropic effects on the cell cycle and their most direct role in inhibition of cholesterol biosynthesis.
authors.affiliation: Division of Cardiology, Scott & White Hospital, Texas A&M HSC College of Medicine, Temple, Texas; Sacred Heart Medical Center/Providence Spokane Heart Institute, Spokane, Washington. Electronic address: nandini.nair@gmail.com.
authors.forename: Nandini
authors.initials: N
authors.lastname: Nair
authors.affiliation: Department of Cardiothoracic Surgery, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, Pennsylvania.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gongora
authors.affiliation: Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Mandeep R
authors.initials: MR
authors.lastname: Mehra
mesh_terms: D014943:Global Health; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D015994:Incidence; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D016377:Organ Transplantation; D013997:Time Factors
keywords: cancers post-induction; post-transplant malignancies; regulatory B cells in tolerance