The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression
Clin. transl. oncol. (Print)
; 24(6): 1157-1167, junio 2022. tab, graf
Artigo
em Inglês
| IBECS
| ID: ibc-203814
Biblioteca responsável:
ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
PurposeA 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 methodsWe 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.ResultsWhole 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.ConclusionNumerous 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 patients constitutional mtDNA manifests the helper T-cell capacity to mount immunity that controls metastatic susceptibility.
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Coleções:
Bases de dados nacionais
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Espanha
Base de dados:
IBECS
Assunto principal:
Neoplasias Retais
/
DNA Mitocondrial
/
Mitocôndrias
Limite:
Humanos
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2022
Tipo de documento:
Artigo
Instituição/País de afiliação:
Akershus University Hospital/Norway
/
Hospital Universitario Akershus/Norway
/
Oslo University Hospital/Norway