Metabolic State Crucial To Immunotherapy-effectiveness

LeeLemonoil

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Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence. - PubMed - NCBI
Response of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence.

Harel M, et al. Cell. 2019.

Abstract
Immunotherapy has revolutionized cancer treatment, yet most patients do not respond. Here, we investigated mechanisms of response by profiling the proteome of clinical samples from advanced stage melanoma patients undergoing either tumor infiltrating lymphocyte (TIL)-based or anti- programmed death 1 (PD1) immunotherapy. Using high-resolution mass spectrometry, we quantified over 10,300 proteins in total and ∼4,500 proteins across most samples in each dataset. Statistical analyses revealed higher oxidative phosphorylation and lipid metabolism in responders than in non-responders in both treatments. To elucidate the effects of the metabolic state on the immune response, we examined melanoma cells upon metabolic perturbations or CRISPR-Cas9 knockouts. These experiments indicated lipid metabolism as a regulatory mechanism that increases melanoma immunogenicity by elevating antigen presentation, thereby increasing sensitivity to T cell mediated killing both in vitro and in vivo. Altogether, our proteomic analyses revealed association between the melanoma metabolic state and the response to immunotherapy, which can be the basis for future improvement of therapeutic response.
 

yerrag

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Altogether, our proteomic analyses revealed association between the melanoma metabolic state and the response to immunotherapy, which can be the basis for future improvement of therapeutic response.

How do interpret the meaning of "melanoma metabolic state?" Is it the metabolic state of the subject with melanoma or is it the metabolic state of the melanoma cells?
 
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LeeLemonoil

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What a sentence:
Immunotherapy revolutionized cancer-therapy !!

but doesn’t work for most ... nice. Surgery successful, Patient dead. Gotta love physicians.

In an case this is heavy Mainstream, multi-billion medicine and they seem to acknowledge metabolic state as the deciding factor.
@haidut and @Amazoniac this worth your precious attention
 
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LeeLemonoil

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Would be good to know what „higher lipid metabolism“ means. Wouldn’t it mean less lipid metabolism in mitos due to better oxphos?
 

yerrag

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Proteome of the individuals with melanoma is my understanding

Thanks. I thought so too. Just seemed pretty obvious but I had to ask.

This is good to know, as it's plain to see for the members of this forum who value the energy of having good metabolism. This is why I question some cancer therapies used to combat cancer where the body is deprived of nutrients. Therapies should consider the body as self-healing and be able to improve the body's ability to heal itself.
 

yerrag

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Would be good to know what „higher lipid metabolism“ means. Wouldn’t it mean less lipid metabolism in mitos due to better oxphos?

That's a good catch.

It probably stems from a view of sugar being cancer's best friend, espoused by mainstream medicine.

In an case this is heavy Mainstream, multi-billion medicine and they seem to acknowledge metabolic state as the deciding factor.
At least they put metabolism in a pedestal lol. Maybe they will just use immunotherapy on patients after screening them. If they have good metabolism, they can use immunotherapy. But this seems like an oxymoron. If you have good metabolism, why would you have cancer? Perhaps they're differentiating only based on a low cut-off - the 10% percentile?
 
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LeeLemonoil

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I tend not to disregard other factors in pathology and therapy in any illness but without some level of functional metabolism all is nothing
 

yerrag

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I tend not to disregard other factors in pathology and therapy in any illness but without some level of functional metabolism all is nothing

That's true, as there are infectious bases of pathology that have to be considered. But even so, if the body has good metabolic health, it can still sustain the insult and recover. Unless the infection is of a unique nature where the body hasn't developed an immunity for.
 

jondoeuk

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Responders had a higher lipid metabolism and mitochondrial respiration in their cancer cells. This improved antigen processing, presentation and IFN signaling which led to better recognition by the immune system.
 
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LeeLemonoil

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Thanks @jondoeuk

So I didn’t really understand the publication.
So then immunotherapy works only in cancer cells with some sort of functioning mitos. That’s complicating it very heavily
 

Cynthia386

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That's a good catch.

It probably stems from a view of sugar being cancer's best friend, espoused by mainstream medicine.


At least they put metabolism in a pedestal lol. Maybe they will just use immunotherapy on patients after screening them. If they have good metabolism, they can use immunotherapy. But this seems like an oxymoron. If you have good metabolism, why would you have cancer? Perhaps they're differentiating only based on a low cut-off - the 10% percentile?
Children typically have great metabolisms. Which means that on the rare occasion a child does get cancer, it is a very aggressive cancer that cannot be handled by a good metabolism/immune system.
 

yerrag

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Children typically have great metabolisms. Which means that on the rare occasion a child does get cancer, it is a very aggressive cancer that cannot be handled by a good metabolism/immune system.
Aren't you falling into a trap and choosing to diagnose based on age? Why not base it on context? You are saying the child has very good metabolism because he is a child, and therefore, based on this, the cancer has to be aggressive that it can overcome the very good metabolism of a child.

Is that child living in a primitive culture or in a mass-propagandized and controlled authoritarian culture of science of high priests by diktat?
 

Cynthia386

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Aren't you falling into a trap and choosing to diagnose based on age? Why not base it on context? You are saying the child has very good metabolism because he is a child, and therefore, based on this, the cancer has to be aggressive that it can overcome the very good metabolism of a child.

Is that child living in a primitive culture or in a mass-propagandized and controlled authoritarian culture of science of high priests by diktat?
I am not diagnosing. I am illustrating the fact that sometimes people with good immune systems/metabolisms get cancer. And when they do it is usually aggressive. Conversely, a lot of the cancers unhealthy people get just go away when they start eating healthy.
 

yerrag

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I am not diagnosing. I am illustrating the fact that sometimes people with good immune systems/metabolisms get cancer. And when they do it is usually aggressive. Conversely, a lot of the cancers unhealthy people get just go away when they start eating healthy.
I could be wrong but it doesn't make sense to me that a person with very good metabolism would develop cancer at all.

If the cause is infection, then the infection would first cause metabolism to be wrecked before cancer develops.

Same thing with toxins, radiation etc.

There is no cancer that is so aggressive that off the bat it would overcome the very good metabolism of a healthy person. It is only aggressive after the body continues to be in a weak state for a budding cancer to keep growing and be termed aggressive.
 

Cynthia386

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I could be wrong but it doesn't make sense to me that a person with very good metabolism would develop cancer at all.

If the cause is infection, then the infection would first cause metabolism to be wrecked before cancer develops.

Same thing with toxins, radiation etc.

There is no cancer that is so aggressive that off the bat it would overcome the very good metabolism of a healthy person. It is only aggressive after the body continues to be in a weak state for a budding cancer to keep growing and be termed aggressive.
Good falls short of being perfect. Still their are stories about tribes where cancer is unknown.
 

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