Heliyon (Nov 2024)

Immunoediting in acute myeloid leukemia: Reappraising T cell exhaustion and the aberrant antigen processing machinery in leukemogenesis

  • Ching-Yun Wang,
  • Shiuan-Chen Lin,
  • Kao-Jung Chang,
  • Han-Ping Cheong,
  • Sin-Rong Wu,
  • Cheng-Hao Lee,
  • Ming-Wei Chuang,
  • Shih-Hwa Chiou,
  • Chih-Hung Hsu,
  • Po-Shen Ko

Journal volume & issue
Vol. 10, no. 21
p. e39731

Abstract

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Acute myeloid leukemia (AML) establishes an immunosuppressive microenvironment that favors leukemic proliferation. The immune-suppressive cytokines altered antigen processing, and presentation collectively assist AML cells in escaping cytotoxic T-cell surveillance. These CD8+ T cell dysfunction features are emerging therapeutic targets in relapsed/refractory AML patients. Besides, CD8+ T cell exhaustion is a hotspot in recent clinical oncology studies, but its pathophysiology has yet to be elucidated in AML. In this review, we summarize high-quality original studies encompassing the phenotypic and genomic characteristics of T cell exhaustion events in the leukemia progression, emphasize the surface immuno-peptidome that dynamically tunes the fate of T cells to function or dysfunction states, and revisit the biochemical and biophysical properties of type 1 MHC antigen processing mechanism (APM) that pivots in the phenomenon of leukemia antigen dampening.