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Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia.
- Source :
- Experimental Hematology & Oncology; 9/6/2024, Vol. 13 Issue 1, p1-15, 15p
- Publication Year :
- 2024
-
Abstract
- Besides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing. Based on the STARTRAC-like algorithm, we defined bystander T cells and tumor-reactive T cells. Compared with bystander T cells, tumor-reactive T cells presented as senescent-like cytotoxic terminally differentiated T cells (Temra) with upregulated NK-related markers. Additionally, we found ADGRG1 could serve as the specific marker of CD8<superscript>+</superscript> T tumor-reactive T cell and validated it through the Runx1<superscript>Runx1t1/+</superscript>; Mx1-Cre mouse model. In chimeric antigen receptor (CAR)-T and target cell system, ADGRG1 was selectively upregulated upon antigen-TCR encounter. Moreover, ADGRG1<superscript>+</superscript>CD8<superscript>+</superscript> T cells released a higher level of IFN-γ and showed higher cell-killing ability when exposed to matched AML blasts. Together, our findings depict the single-cell profile of tumor-reactive T cells in AML BM and propose that ADGRG1 can act as an indicator of T cell tumor reactivity in AML, which may be further harnessed for adoptive cell therapy and tumor-reactive TCR enrichment. Key points: 1. CD8<superscript>+</superscript> tumor-reactive T cells present in AML BM and are characterized as senescent-like cytotoxic Temra with upregulated NK-related markers. 2. ADGRG1 can serve as a specific marker of CD8<superscript>+</superscript> tumor-reactive T cells in AML BM. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21623619
- Volume :
- 13
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Experimental Hematology & Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 179506204
- Full Text :
- https://doi.org/10.1186/s40164-024-00560-0