How cancer cells resist immune attack

How cancer cells resist immune attack

Human melanoma cells express various tumor antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTLs) and elicit tumor-specific responses in vivo. Clinical trials based on the induction of antigen-specific CTL responses against tumor cells have been reported in various types of cancer. 

However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying CTL effector phase failure when facing melanomas are still largely elusive.

Researchers show that, on conjugation with CTL, human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration.
Impairment of lysosomal proteolytic activity by different means restores susceptibility to CTL attack.

Inside the arsenal of melanoma cell strategies to escape immune surveillance, authors identify a self-defence mechanism based on exacerbated lysosome secretion and perforin degradation at the lytic synapse. Interfering with this synaptic self-defence mechanism might be useful in potentiating CTL-mediated therapies in melanoma patients.

http://www.nature.com/ncomms/2016/160304/ncomms10823/full/ncomms10823.html

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