دورية أكاديمية
أعرض في EDS

The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression.

التفاصيل البيبلوغرافية
العنوان: The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression.
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
الوصف
تدمد:1699-3055
DOI:10.1007/s12094-021-02756-w