دورية أكاديمية
The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression.
العنوان: | The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression. |
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المؤلفون: | Bousquet PA; Department of Oncology, Akershus University Hospital, Lorenskog, Norway., Meltzer S; Department of Oncology, Akershus University Hospital, Lorenskog, Norway., Fuglestad AJ; Department of Oncology, Akershus University Hospital, Lorenskog, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Centre for Cancer Treatment, Sørlandet Hospital, Kristiansand, Norway., Lüders T; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Clinical Molecular Biology, Akershus University Hospital, Lorenskog, Norway., Esbensen Y; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Clinical Molecular Biology, Akershus University Hospital, Lorenskog, Norway., Juul HV; Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Johansen C; Department of Oncology, Akershus University Hospital, Lorenskog, Norway., Lyckander LG; Department of Pathology, Akershus University Hospital, Lorenskog, Norway., Bjørnetrø T; Department of Oncology, Akershus University Hospital, Lorenskog, Norway., Inderberg EM; Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway., Kersten C; Department of Oncology, Akershus University Hospital, Lorenskog, Norway.; Centre for Cancer Treatment, Sørlandet Hospital, Kristiansand, Norway., Redalen KR; Department of Oncology, Akershus University Hospital, Lorenskog, Norway.; Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway., Ree AH; Department of Oncology, Akershus University Hospital, Lorenskog, Norway. a.h.ree@medisin.uio.no.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. a.h.ree@medisin.uio.no. |
المصدر: | Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2022 Jun; Vol. 24 (6), pp. 1157-1167. Date of Electronic Publication: 2021 Dec 27. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Country of Publication: Italy NLM ID: 101247119 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1699-3055 (Electronic) Linking ISSN: 1699048X NLM ISO Abbreviation: Clin Transl Oncol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2010- >: Milan : Springer Italia Original Publication: Barcelona, Spain : Doyma, c2005- |
مواضيع طبية MeSH: | DNA, Mitochondrial*/genetics , Rectal Neoplasms*/genetics, Humans ; Mitochondria/genetics ; Prospective Studies |
مستخلص: | Purpose: A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate of energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. Patients and Methods: We studied 44 rectal cancer patients from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation and radical surgery for high-risk tumour stage and followed for metastatic failure. Blood specimens were sampled at the time of diagnosis and analysed for the full-length mtDNA sequence, composition of immune cell subpopulations and damaged serum mtDNA. Results: Whole blood total mtDNA variant number above the median value for the study cohort, coexisting with an mtDNA non-H haplogroup, was representative for the mtDNA of circulating immune cells and associated with low risk of a metastatic event. Abundant mtDNA variants correlated with proliferating helper T cells and cytotoxic effector T cells in the circulation. Patients without metastatic progression had high relative levels of circulating tumour-targeting effector T cells and, of note, the naïve (LAG-3 + ) helper T-cell population, with the proportion of LAG-3 + cells inversely correlating with cell-free damaged mtDNA in serum known to cause antagonising inflammation. Conclusion: Numerous mtDNA polymorphisms in peripheral blood reflected clonal expansion of circulating helper and cytotoxic T-cell populations in patients without metastatic failure. The statistical associations suggested that patient's constitutional mtDNA manifests the helper T-cell capacity to mount immunity that controls metastatic susceptibility. Trial Registration: ClinicalTrials.gov NCT01816607; registration date: 22 March 2013. (© 2021. The Author(s).) |
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معلومات مُعتمدة: | 5740692 Kreftforeningen; 2018054 Helse Sør-Øst RHF; 2019109 Helse Sør-Øst RHF |
فهرسة مساهمة: | Keywords: CD4; Colorectal cancer; Immune cells; Metastasis; Mitochondrial DNA |
سلسلة جزيئية: | ClinicalTrials.gov NCT01816607 |
المشرفين على المادة: | 0 (DNA, Mitochondrial) |
تواريخ الأحداث: | Date Created: 20211228 Date Completed: 20220517 Latest Revision: 20230916 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9107448 |
DOI: | 10.1007/s12094-021-02756-w |
PMID: | 34961902 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1699-3055 |
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DOI: | 10.1007/s12094-021-02756-w |