Cancers Related to Immunodeficiencies: Update and Perspectives

Abstract

The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with posttransplantation immune dysfunction, with immunosuppressive medication for human immunodeficiency virus or with human T-cell lymphotropic virus infection. After infection, malignancy is the most prevalent cause of death in both children and adults with (PIDs). PIDs more often associated with cancer include common variable immunodeficiency (CVID), Wiskott–Aldrich syndrome, ataxia-telangiectasia, and severe combined immunodeficiency. This suggests that a protective immune response against both infectious non-self-(pathogens) and malignant self-challenges (cancer) exists. The increased incidence of cancer has been attributed to defective elimination of altered or “transformed” cells and/or defective immunity towards cancer cells. The concept of aberrant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies and the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.

Common variable immune deficiency: Dissection of the variable

“…Individuals with CVID are susceptible to malignancy, and have an estimated 1.8‐ to 5‐fold increased risk of developing cancers of all types . Estimates for lymphoma are higher, possibly 30 times greater than in control populations and in one study, were more common in women .…”

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

“…GLILD (usually presenting in CVID), chronic granulomatous disease, and immune dysregulation (including hemophagocytic lymphohistiocytosis and autoimmune lymphoproliferative syndrome) are common lymphoproliferative PIDs associated with pulmonary adenopathies. Primary lymphoma (extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue due to increased genetic vulnerability to Epstein-Barr virus-induced complications) [120,121] and secondary lung metastatic malignancy (in PAD and CID patients with DNA repair system defects, NK-cell defects, and cytotoxic T-cell defects) may present initially with thoracic adenopathy [122][123][124]. Infiltration of the lung with metastases and subsequent restrictive disease is more common than primary lung tumors.…”

Wiskott-Aldrich syndrome gene mutations modulate cancer susceptibility in the p53±murine model

“…1 The reason for increased cancer risk could be failure of the immune system to eradicate tumors or due to intrinsic failure during myelopoiesis and lymphopoiesis. Mutations in the WAS gene that encodes for the cytoskeletal regulator WASp are associated with two immunodeficiency syndromes, Wiskott-Aldrich syndrome (WAS) and X-linked neutropenia (XLN).…”