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

doi:10.1016/j.heliyon.2024.e39731

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

Heliyon. 2024 Oct 25;10(21):e39731. doi: 10.1016/j.heliyon.2024.e39731. eCollection 2024 Nov 15.

Authors

Ching-Yun Wang¹, Shiuan-Chen Lin^{2

3}, Kao-Jung Chang^{2

3

4

5}, Han-Ping Cheong^{3

6}, Sin-Rong Wu³, Cheng-Hao Lee³, Ming-Wei Chuang³, Shih-Hwa Chiou^{2

3

4

5

6

7}, Chih-Hung Hsu⁸, Po-Shen Ko^{2

9}

Affiliations

¹ Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan.
² School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
³ Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
⁵ Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶ Institute of Pharmacology, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
⁷ Genomic Research Center, Academia Sinica, Taipei, Taiwan.
⁸ Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, China.
⁹ Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Abstract

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.

Publication types

Review