T cells in AML are not uniformly dysfunctional, researchers argue in new analysis

Acute myeloid leukemia remains one of the most difficult blood cancers to control, and a new debate article published in BMC Medicine argues that part of the problem lies in how researchers judge the immune cells meant to fight it. The authors, led by Zoi Katana and Sébastien Anguille, contend that T cells in AML are not uniformly dysfunctional, and that the field’s reliance on a single marker of T cell exhaustion has produced an incomplete and potentially misleading picture of immune failure in this disease.

AML is an aggressive cancer marked by uncontrolled proliferation of myeloid blasts in the bone marrow. Treatment of newly diagnosed patients is guided by fitness and molecular risk stratification, drawing on intensive chemotherapy, venetoclax-based regimens, targeted therapies and, in selected patients, allogeneic hematopoietic stem cell transplantation. Yet despite initial responses, relapse is frequent, and the five-year survival rate remains below 30 percent. A factor linked to relapse is T cell exhaustion and dysfunction, particularly after stem cell transplantation.

The core of the authors’ argument is methodological. T cell exhaustion is commonly assessed solely on the expression of inhibitory receptors such as PD-1, TIM-3, LAG-3 and CTLA-4. According to the article, this provides an incomplete picture of T cell impairment, because receptor expression alone does not fully capture whether a T cell can actually perform its anti-leukemic work.

To close that gap, the authors propose a more comprehensive and standardized definition of T cell functionality that extends beyond inhibitory receptor expression. Their framework would encompass cytokine secretion and cytotoxic capacity, activation and proliferative potential, metabolic profile, T cell subset composition, telomere length and epigenetic state. Multiparameter characterization of this kind, they argue, enables a deeper assessment of T cell functionality in AML than any single surface marker.

Central to the article is the claim that T cells in AML display heterogeneous functional states. Based on emerging data, the authors argue that many T cells retain cytotoxic potential despite evidence of context-dependent dysfunction. In other words, impairment in AML is not a uniform shutdown of the immune response but a variable, environmentally shaped condition that differs across patients and disease settings.

The authors examine how the AML tumor microenvironment can drive T cell impairment, framing dysfunction as context-dependent rather than intrinsic and irreversible. The authors argue that this reframing challenges prevailing assumptions in the field and opens new therapeutic opportunities.

The practical stakes are considerable. The authors argue that integrating functional, metabolic and epigenetic insights into T cell profiling will be critical for the rational design, timing and optimization of T cell-based therapies in AML, with the potential to overcome immune failure and improve durable disease control. A deeper, standardized, multidimensional understanding of T cell functional heterogeneity is described as essential for advancing immunotherapy in this disease.

The article is published as an open access debate piece, dated 27 October 2026, and is being shared early as a peer-reviewed, accepted manuscript that is citable and carries a permanent DOI, subject to further edits before the final version of record. As a debate article, it does not report new clinical trial results but synthesizes existing evidence into a position statement about how T cell function should be measured in AML research and immunotherapy development.

For clinicians and immunotherapy developers, the message is that the tools used to define T cell exhaustion may themselves need updating. The authors’ proposed multidimensional profiling standard is offered as a step toward more reliable interpretation of immune failure in AML and better-informed decisions about when and how to deploy T cell-based treatments.

Subject of Research: Functional characterization of T cell dysfunction in acute myeloid leukemia

Article Title: T cells in AML: are they functionally impaired? a call for comprehensive characterization

Article References: Katana, Z., Campillo-Davo, D., Berneman, Z. N., & Anguille, S. (2026). T cells in AML: are they functionally impaired? a call for comprehensive characterization. BMC Medicine. https://doi.org/10.1186/s12916-026-05319-4

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05319-4

Keywords: acute myeloid leukemia, T cell exhaustion, inhibitory receptors, PD-1, tumor microenvironment, immunotherapy, T cell dysfunction, cytotoxicity, epigenetics, hematopoietic stem cell transplantation, BMC Medicine, cells