Immune-driven clonal cell selection at the intersection among cancer, infections, autoimmunity and senescence

Semin Hematol. 2024 Feb;61(1):22-34. doi: 10.1053/j.seminhematol.2024.01.002. Epub 2024 Jan 17.

Abstract

Immune surveillance mechanisms play a crucial role in maintaining lifelong immune homeostasis in response to pathologic stimuli and aberrant cell states. However, their persistence, especially in the context of chronic antigenic exposure, can create a fertile ground for immune evasion. These escaping cell phenotypes, harboring a variety of genomic and transcriptomic aberrances, chiefly in human leukocyte antigen (HLA) and antigen presentation machinery genes, may survive and proliferate, featuring a scenario of clonal cell expansion with immune failure characteristics. While well characterized in solid and, to some extent, hematological malignancies, little is known about their occurrence and significance in other disease contexts. Historical literature highlights the role for escaping HLA-mediated recognition as a strategy adopted by virus to evade from the immune system, hinting at the potential for immune aberrant cell expansion in the context of chronic infections. Additionally, unmasked in idiopathic aplastic anemia as a mechanism able to rescue failing hematopoiesis, HLA clonal escape may operate in autoimmune disorders, particularly in tissues targeted by aberrant immune responses. Furthermore, senescent cell status emerging as immunogenic phenotypes stimulating T cell responses, may act as a bottleneck for the selection of such immune escaping clones, blurring the boundaries between neoplastic transformation, aging and inflammation. Here we provide a fresh overview and perspective on this immune-driven clonal cell expansion, linking pathophysiological features of neoplastic, autoimmune, infectious and senescence processes exposed to immune surveillance.

Keywords: Autoimmunity; CHIP; Cancer; Clonal immune escape; Immune evasion; Immunoediting; Infections; Senescence.

MeSH terms

  • Anemia, Aplastic*
  • Autoimmune Diseases*
  • Autoimmunity
  • Clone Cells / pathology
  • HLA Antigens
  • Humans
  • Neoplasms* / genetics

Substances

  • HLA Antigens