Abstract
Because of its disseminated nature and lack of tumor-draining lymph nodes, acute myeloid leukemia (AML) likely employs unique immune evasion strategies as compared to solid malignancies. Targeting these unique mechanisms may result in improved immunotherapeutic approaches. Emerging data suggest that a specific dendritic cell (DC) subset, CD8α DCs, may be responsible for mediating tolerance in AML and thus targeting the innate immune system may be of benefit in this disease. Promising immune targets include the toll-like receptors, calreticulin/CD47, the stimulator of interferon genes pathway, and signal transducer and activator of transcription 3 (STAT3). However, it is becoming clear that compensatory mechanisms may limit the efficacy of these agents alone and thus rationale combinations of immunotherapies are warranted. This review discusses the potential immune evasion strategies in AML, as well as discussion of the promising innate immune targets, both alone and in combination, for this disease.
Highlights
Over 18,000 people will be diagnosed with acute myeloid leukemia (AML) in the United States this year [1]
Allogeneic stem cell transplantation can be curative for some patients with AML [3], thought to be secondary to therapeutic graft-versusleukemia effects resulting from donor-derived T cell recognition of minor histocompatibility antigens expressed on host leukemia cells [3,4,5,6]
It is known that AML cells express leukemia-associated antigens (LAA) that can be recognized by the immune system, including those derived from proteins such as proteinase 3 (PR3), receptor for hyaluronic acid-mediated motility (RHAMM), and Wilm’s tumor-1 (WT1), among others [7, 8]
Summary
Over 18,000 people will be diagnosed with acute myeloid leukemia (AML) in the United States this year [1]. Poly(I:C) is currently being investigated as an adjuvant to vaccine therapy in an early phase clinical trial in patients with AML in complete remission following chemotherapy or allogeneic stem cell transplantation (Table 1) This trial combines a WT1 peptide vaccine with basiliximab and either poly(I:C) or montanide ISA 51, with the goal of determining the side effects and best method of administering vaccine therapy. Some chemotherapeutic agents (anthracyclines and oxaliplatin) and radiation have been shown to induce ER stress and promote CRT surface translocation in cancer cells, resulting in their recognition and phagocytosis by innate immune cells, such as macrophages and DCs [44] These innate immune cells become capable of priming antigen-specific T cell responses directed against malignant cells, termed “immunologic cell death.”. Using publicly available gene profiling data sets, Chao analyzed CRT mRNA levels in tumors from patients with a variety of cancers, including neuroblastoma, bladder cancer, and mantle cell lymphoma and found, perhaps counterintuitively, that elevated CRT expression correlated inversely with event-free and/or overall survival [45]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
