The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Carl Borrebaeck

Carl Borrebaeck


Carl Borrebaeck

Transcriptional profiling demonstrates altered characteristics of CD8 + cytotoxic T-cells and regulatory T-cells in TP53-mutated acute myeloid leukemia


  • Milad Abolhalaj
  • Viktor Sincic
  • Henrik Lilljebjörn
  • Carl Sandén
  • Alar Aab
  • Karin Hägerbrand
  • Peter Ellmark
  • Carl Borrebaeck
  • Thoas Fioretos
  • Kristina Lundberg

Summary, in Swedish

Background: Acute myeloid leukemia (AML) patients have limited effect from T-cell-based therapies, such as PD-1 and CTLA-4 blockade. However, recent data indicate that AML patients with TP53 mutation have higher immune infiltration and other immunomodulatory therapies could thus potentially be effective. Here, we performed the transcriptional analysis of distinct T-cell subpopulations from TP53-mutated AML to identify gene expression signatures suggestive of altered functional properties.

Methods: CD8+ cytotoxic T lymphocytes (CTLs), conventional helper T cells (Th), and regulatory T cells (Tregs) were sorted from peripheral blood of AML patients with TP53 mutation (n = 5) and healthy donors (n = 3), using FACS, and the different subpopulations were subsequently subjected to RNA-sequencing. Differentially expressed genes were identified and gene set enrichment analysis (GSEA) was performed to outline altered pathways and exhaustion status. Also, expression levels for a set of genes encoding established and emerging immuno-oncological targets were defined.

Results: The results showed altered transcriptional profiles for each of the T-cell subpopulations from TP53-mutated AML as compared to control subjects. IFN-α and IFN-γ signaling were stronger in TP53-mutated AML for both CTLs and Tregs. Furthermore, in TP53-mutated AML as compared to healthy controls, Tregs showed gene expression signatures suggestive of metabolic adaptation to their environment, whereas CTLs exhibited features of exhaustion/dysfunction with a stronger expression of TIM3 as well as enrichment of a gene set related to exhaustion.

Conclusions: The results provide insights on mechanisms underlying the inadequate immune response to leukemic cells in TP53-mutated AML and open up for further exploration toward novel treatment regimens for these patients.


  • LUCC: Lund University Cancer Centre
  • Department of Immunotechnology
  • Create Health
  • Biotechnology (M.Sc.Eng.)
  • Translational Genomic and Functional Studies of Leukemia
  • Division of Clinical Genetics

Publishing year







Cancer Medicine





Document type

Journal article




  • Immunology in the medical area
  • Cancer and Oncology


  • T-cell
  • RNA-Sequencing
  • acute myeloid leukemia (AML)
  • TP53
  • Immunotherapy



Research group

  • Translational Genomic and Functional Studies of Leukemia


  • ISSN: 2045-7634