Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):287-295. doi: 10.1182/hematology.2021000261.
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.
免疫缺陷无论是由人类免疫缺陷病毒（HIV）感染引起的获得性免疫缺陷，还是由先天性免疫缺陷（IEI）引起的，其临床表现不仅包括感染和免疫失调，还包括恶性肿瘤风险增加。所见到的恶性肿瘤范围相对有限，归因于每种疾病中特定的细胞和分子缺陷。HIV 感染者（PLWH）和某些 IEI 中的 CD4+T 细胞淋巴细胞减少会导致侵袭性 B 细胞非霍奇金淋巴瘤的易感性增加，包括某些在免疫功能正常个体中很少见的罕见亚型。导致严重 T 细胞淋巴细胞减少或功能障碍的 PLWH 和 IEI 也有罹患与致癌病毒相关的癌症的风险，如卡波西肉瘤疱疹病毒、EB 病毒、人乳头瘤病毒（HPV）和 Merkel 细胞多瘤病毒。影响自然杀伤细胞发育和/或功能的 IEI 会强烈导致 HPV 相关上皮癌。除了影响造血和上皮细胞的 DNA 损伤反应外，DNA 修复途径的缺陷还会在免疫受体重排期间影响 T 和 B 淋巴细胞的发育，导致血液系统和非血液系统癌症。免疫缺陷个体的癌症治疗应具有治愈意图，并与免疫学和传染病领域的疾病专家密切协商进行。
