Elucidating the Role of the T Cell Receptor Repertoire in Myelodysplastic Neoplasms and Acute Myeloid Leukemia

Abstract

T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies. Myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are hematological neoplasms that are characterized by immune evasion mechanisms, with immunotherapy giving only modest results thus far. Our review of TCR repertoire dynamics in these diseases reveals distinct patterns: MDS patients show increased TCR clonality with disease progression, while AML exhibits varied TCR signatures depending on disease stage and treatment response. Understanding these patterns has important clinical implications, as TCR repertoire metrics may serve as potential biomarkers for disease progression and treatment response, particularly in the context of immunotherapy and stem cell transplantation. These insights could guide patient stratification and treatment selection, ultimately improving therapeutic outcomes in MDS and AML.

Keywords: T cell receptor; TCR repertoire; acute myeloid leukemia; hematopoietic stem cell transplantation; immunotherapy; myelodysplastic syndromes.

Figure 1

Schematic diagram illustrating the V(D)J recombination process of the β chain (A) and an assembled TCRαβ (Β). Constant regions and gene segments (C) are represented in light blue. Variable (V), diversity (D), and joining (J) are shown in orange, dark blue, and yellow, respectively. Created in BioRender. Barakos, G. https://BioRender.com/d60w564 (accessed on 3 December 2024).

Figure 2

Representation of TCR repertoire dynamics in the natural history of MDS and AML. A skewed TCR response in diagnosis is followed either by increased diversity and novel clonotypes (during therapy response) or further reduction in TCR diversity and clonal hyperexpansion (in relapsed/refractory disease). Allo-HSCT effects on TCR repertoire are variable and interrelated with outcome. Different colored T cells represent different clonotypes, and different colored myeloid cancer cells represent phenotypes of disease stages. Created in BioRender. Barakos, G., https://BioRender.com/l59m745 (accessed on 3 December 2024).

Figure 3

The integration of artificial intelligence (AI) and machine learning (ML) may transform the TCR repertoire analysis and contribute to personalized treatment.