How immunodeficiency can lead to malignancy

Abstract

Immunodeficiency, whether acquired in the case of human immunodeficiency virus (HIV) infection or congenital due to inborn errors of immunity (IEIs), presents clinically with not only infection and immune dysregulation but also increased risk of malignancy. The range of malignancies seen is relatively limited and attributable to the particular cellular and molecular defects in each disease. CD4+ T-cell lymphopenia in people living with HIV infection (PLWH) and certain IEIs drive the predisposition to aggressive B-cell non-Hodgkin lymphomas, including certain rare subtypes rarely seen in immunocompetent individuals. PLWH and IEI that lead to profound T-cell lymphopenia or dysfunction also are at risk of cancers related to oncogenic viruses such as Kaposi sarcoma herpesvirus, Epstein-Barr virus, human papillomavirus (HPV), and Merkel cell polyomavirus. IEIs that affect natural killer cell development and/or function heavily predispose to HPV-associated epithelial cancers. Defects in DNA repair pathways compromise T- and B-lymphocyte development during immune receptor rearrangement in addition to affecting hematopoietic and epithelial DNA damage responses, resulting in both hematologic and nonhematologic cancers. Treatment of cancers in immunodeficient individuals should be curative in intent and pursued in close consultation with disease experts in immunology and infectious disease.

Risk of thyroid neoplasms in patients with 22q11.2 deletion and DiGeorge-like syndromes: an insight for follow-up

“…As widely described for HIV infection, T lymphopenia or reduced natural killer cells, as well as their dysfunction, may predispose to poor surveillance against neoplastic cells. T-cell dysfunction can also lead to B-cell hyperproliferation and overactivation resulting in a higher risk of developing lymphomas ( 38 , 39 ). In fact, cases of B lymphoma in patients with 22q11.2DS and severe T-cell impairment have been reported in the literature in the past ( 40 , 41 ).…”

Regulator of telomere elongation helicase 1 gene and its association with malignancy

“… 108 , 109 , 110 Furthermore, immunodeficiency, whether congenital or acquired, is associated with an increased risk of malignancy. 111 Similarly, the presence of age‐related chronic inflammation and immunosenescence may significantly affect the development of malignancies in frail individuals. 112 In contrast, certain anti‐inflammatory drugs 113 , 114 and immunotherapies 115 ; have been proven to be effective in treating malignancies.…”

“…Previous studies have indicated that chronic inflammation may play a role in the development and progression of cancer 108–110 . Furthermore, immunodeficiency, whether congenital or acquired, is associated with an increased risk of malignancy 111 . Similarly, the presence of age‐related chronic inflammation and immunosenescence may significantly affect the development of malignancies in frail individuals 112 .…”

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma—a retrospective cohort study

“…It is not yet known whether there is a correlation between lymphocytopenia and poor survival and an association between the specific subset of lymphocytes and inferior prognosis. Previous studies have reported that lymphopenia is an adverse prognostic factor in various solid tumors, Hodgkin's lymphoma (HL), and NHL (24)(25)(26)(27).…”