Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy.

Autor: Abbas HA; Division of Cancer Medicine, Medical Oncology Fellowship, University of Texas M D Anderson Cancer Center, Houston, TX, USA.; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hao D; Division of Cancer Medicine, Medical Oncology Fellowship, University of Texas M D Anderson Cancer Center, Houston, TX, USA.; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Tomczak K; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Barrodia P; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Im JS; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Reville PK; Division of Cancer Medicine, Medical Oncology Fellowship, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Alaniz Z; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang W; Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang R; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Wang F; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Al-Atrash G; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Takahashi K; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Ning J; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ding M; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Statistics, Rice University, Houston, TX, USA., Beird HC; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Mathews JT; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Little L; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Zhang J; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA., Basu S; Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Konopleva M; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Marques-Piubelli ML; Department Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Solis LM; Department Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Parra ER; Department Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lu W; Department Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tamegnon A; Department Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Garcia-Manero G; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Green MR; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA.; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sharma P; Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Allison JP; Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kornblau SM; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Rai K; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA. KRai@mdanderson.org., Wang L; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA. lwang22@mdanderson.org.; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. lwang22@mdanderson.org., Daver N; Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA. NDaver@mdanderson.org., Futreal A; Department of Genomic Medicine, University of Texas M D Anderson Cancer Center, Houston, TX, USA. AFutreal@mdanderson.org.; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. AFutreal@mdanderson.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Oct 18; Vol. 12 (1), pp. 6071. Date of Electronic Publication: 2021 Oct 18.
DOI: 10.1038/s41467-021-26282-z
Abstrakt: In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8 + cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy - resistant patients. Trajectory analysis reveals a continuum of CD8 + T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8 + T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.
(© 2021. The Author(s).)
Databáze: MEDLINE
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