دورية أكاديمية
Hallmarks of tumor-experienced T cells are absent in multiple myeloma patients from diagnosis through maintenance therapy.
| العنوان: | Hallmarks of tumor-experienced T cells are absent in multiple myeloma patients from diagnosis through maintenance therapy. |
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| المؤلفون: | Shasha C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Glass DR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Moelhman E; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Islas L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Tian Y; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Szeto GL; Allen Institute for Immunology, Seattle, WA, USA., Peng T; Allen Institute for Immunology, Seattle, WA, USA., Song X; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Wurscher M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA., Bumol TF; Allen Institute for Immunology, Seattle, WA, USA., Torgerson TR; Allen Institute for Immunology, Seattle, WA, USA., Greenberg PD; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA.; Department of Immunology, University of Washington, Seattle, WA, USA., Green DJ; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Newell EW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 04. Date of Electronic Publication: 2024 Jun 04. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Dysregulation of the bone marrow (BM) niche in multiple myeloma (MM) alters the composition and state of resident immune cells, potentially impeding anti-tumor immunity. One common mechanism of immune inhibition in solid tumors is the induction of exhaustion in tumor-specific T cells. However, the extent of T cell tumor recognition and exhaustion is not well-characterized in MM. As the specific mechanisms of immune evasion are critical for devising effective therapeutic strategies, we deeply profiled the CD8 + T cell compartment of newly-diagnosed MM (NDMM) patients for evidence of tumor reactivity and T cell exhaustion. We applied single-cell multi-omic sequencing and antigen-specific mass cytometry to longitudinal BM and peripheral blood (PB) samples taken from timepoints spanning from diagnosis through induction therapy, autologous stem cell transplant (ASCT), and maintenance therapy. We identified an exhausted-like population that lacked several canonical exhaustion markers, was not significantly enriched in NDMM patients, and consisted of small, nonpersistent clones. We also observed an activated population with increased frequency in the PB of NDMM patients exhibiting phenotypic and clonal features consistent with homeostatic, antigen-nonspecific activation. However, there was no evidence of "tumor-experienced" T cells displaying hallmarks of terminal exhaustion and/or tumor-specific activation/expansion in NDMM patients at any timepoint. Competing Interests: CONFLICT OF INTEREST DISCLOSURES G.S. is an employee of, and holds equity in, Pfizer. T.F.B. is a board member at Tentarix Biotherapeutics. P.D.G. is an advisor and shareholder of Immunoscape, Fibrogen, Earli, Elpiscience Biopharmaceuticals, Rapt Therapeutics, Nextech, and Catalio, and is a co-founder, advisor and shareholder of Affini-T Therapeutics. D.J.G . has received research funding, has served as an advisor and has received royalties from Juno Therapeutics, a Bristol-Myers Squibb company; has served as an advisor and received research funding from Janssen Biotech and Seattle Genetics; has served as an advisor for GlaxoSmithKline, Celgene, Ensoma and Legend Biotech; and has received research funding from SpringWorks Therapeutics, Sanofi, and Cellectar Biosciences. E.W.N. is a co-founder, advisor, and shareholder of ImmunoScape and is an advisor for Neogene Therapeutics and NanoString Technologies. All other authors declare no competing interests. |
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| معلومات مُعتمدة: | P01 CA018029 United States CA NCI NIH HHS; UL1 TR002319 United States TR NCATS NIH HHS |
| تواريخ الأحداث: | Date Created: 20240619 Latest Revision: 20240626 |
| رمز التحديث: | 20240626 |
| مُعرف محوري في PubMed: | PMC11185627 |
| DOI: | 10.1101/2024.06.03.597178 |
| PMID: | 38895348 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.06.03.597178 |
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