Convergent science, precision immunotherapy, and ‘bench’ with ‘bedside’ approaches indicate the future of cancer research
“Precision oncology has enabled progress in treatments focusing on actionable gene mutations. However, the vast majority of cancers do not have druggable oncogene mutations. In order for precision oncology to progress further, it must develop to incorporate more aspects of treatment and not focus solely on genetics.”
https://www.future-science.com/doi/10.2 ... -2019-0095
Convergent science, precision immunotherapy, and ‘bench’ with ‘bedside’ approaches indicate future of cancer research
Re: Convergent science, precision immunotherapy, and ‘bench’ with ‘bedside’ approaches indicate future of cancer researc
Bench with bedside
A team of Stanford University (CA, USA) researchers had previously demonstrated that PD-L1 and CD47 proteins are both used by cancer cells to hide from immune cells. Now, treatments that target PD-L1 or its receptor are being used in the clinic, while antibodies that target CD47 are in clinical trials.
Most recently, the Stanford team has reported the discovery of CD24 – a protein also displayed on the surface of cancer cells to signal to macrophages not to engulf them – in Nature [7].
“Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don't eat me’ signals,” commented senior author Irving Weissman [8].
By searching for proteins that were more abundant in cancers than in the tissue from which those cancers arose, the team found increased levels of production of CD24. Probing further, they uncovered that macrophages sense the presence of CD24 through the SIGLEC-10 receptor. When this interaction was blocked in vitro, macrophages would proceed to engulf cancer cells.
“When we imaged the macrophages after treating the cancers with CD24 blockade, we could see that some of them were just stuffed with cancer cells,” revealed first author Amira Barkal.
A team of Stanford University (CA, USA) researchers had previously demonstrated that PD-L1 and CD47 proteins are both used by cancer cells to hide from immune cells. Now, treatments that target PD-L1 or its receptor are being used in the clinic, while antibodies that target CD47 are in clinical trials.
Most recently, the Stanford team has reported the discovery of CD24 – a protein also displayed on the surface of cancer cells to signal to macrophages not to engulf them – in Nature [7].
“Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative ‘don't eat me’ signals,” commented senior author Irving Weissman [8].
By searching for proteins that were more abundant in cancers than in the tissue from which those cancers arose, the team found increased levels of production of CD24. Probing further, they uncovered that macrophages sense the presence of CD24 through the SIGLEC-10 receptor. When this interaction was blocked in vitro, macrophages would proceed to engulf cancer cells.
“When we imaged the macrophages after treating the cancers with CD24 blockade, we could see that some of them were just stuffed with cancer cells,” revealed first author Amira Barkal.
Last edited by D.ap on Sat Aug 10, 2019 6:02 pm, edited 1 time in total.
Debbie
Re: Convergent science, precision immunotherapy, and ‘bench’ with ‘bedside’ approaches indicate future of cancer researc
CD24 and Siglec-10 selectively repress tissue damage–induced immune responses
“Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor κB (NF-κB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24–Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.”
https://scholar.google.com/scholar?q=SI ... AXx3GbB8gJ
“Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor κB (NF-κB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24–Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.”
https://scholar.google.com/scholar?q=SI ... AXx3GbB8gJ
Last edited by D.ap on Sun Aug 11, 2019 8:10 am, edited 1 time in total.
Debbie
Re: Convergent science, precision immunotherapy, and ‘bench’ with ‘bedside’ approaches indicate future of cancer researc
The present antigens studies , specific to ASPS.: )
https://www.cureasps.org/forum/viewtopi ... ent#p12577
https://www.cureasps.org/forum/viewtopi ... ent#p12577
Debbie