Impaired Antigen Presentation in Neoplasia: Basic Mechanisms and Implications for Acute Myeloid Leukemia

Abstract

During onset, treatment and progression of acute myeloid leukemia (AML), inadequate immune responses against certain myeloid leukemic blasts might be associated with the occurrence of minimal residual disease and subsequent relapse. Several studies on this subject have demonstrated that, in general, solid tumor cells are able to avoid CD8⁺ cytotoxic T-cell recognition by downregulating HLA class I-restricted presentation of tumor-associated antigens. In tumor cells that can express HLA class II molecules, such as myeloid leukemic blasts, abnormalities in the processing pathways of endogenous antigens could also result in impaired HLA class II-restricted tumor-associated antigen presentation to CD4⁺ T helper cells. More insight into impaired tumor-associated antigen presentation by myeloid leukemic blasts could explain their escape from immune recognition and might be crucial for selecting appropriate strategies to improve whole-cell or dendritic cell-based tumor vaccine efficacy in the treatment of AML patients.

KEYWORDS::

• antigen processing
• HLA class I
• HLA class II
• immune escape
• immunomodulation
• leukemic blast
• MHC
• myeloid neoplasia
• tumor-associated antigen
• tumor cell

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.