Amazing stuff! Cancer is history (soon)!
"Cancer cells can sabotage immune cells that try to attack them by filling them with defective mitochondria, the organelles that cells rely on to make energy. In samples from three people with cancer, researchers noticed that mitochondria in both the tumour cells and immune cells called tumour-infiltrating lymphocytes (TILs) shared the same mutations. When they grew cancer cells with fluorescent-tagged mitochondria alongside TILs, the TILs had taken on some faulty mitochondria after only 24 hours. By 15 days, their native mitochondria had been replaced almost entirely. Tainted TILs were less able to divide and more likely to commit cell ‘suicide’."
"Cancer cells can poison attacking immune cells by filling them with defective mitochondria ― dampening the body’s defensive forces and helping the tumour to evade eradication. ..."
From the abstract:
"Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack.
For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumor immune responses. However, detailed mechanisms of such processes remain unclear.
Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs.
Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement.
T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation.
This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies."
Cancer cells ‘poison’ the immune system with tainted mitochondria "Immune cells lose their cancer-fighting prowess after taking tumours’ organelles on board."
Fig. 1: TILs and cancer cells share mtDNA-mutated mitochondria.
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