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[r06ue1]

Immunotherapy Pioneer James Allison Has Unfinished Business with Cancer

https://www.technolo...ss-with-cancer/

[scuba]

Excellent reading. I have believed for so long and have stated on this forum that "cancer" results from a failure of our immune system to check it. The responsibility for checking/stopping cancer is the mighty T-cell. James Allison's research highlights not just how T-cells in our bodies work to fight disease, but how turning them on and off in targeting their impact is critical to success.

 

Not mentioned in the article is the fact that cancer cells are "smart" - they have the advantage of being part of the home team sort of speak. They are not foreign to our bodies - they came from us in the first place. Cancer cells give off proteins that tell T-cells to stand down - don't attack. This is critical. T-cells have to be able to stand down so that auto-immune attacks don't happen. Killer T-cells love to kill - and only our normal body cells are able to tell them to stand down after an attack on a foreign body is done. Cancer cells give off proteins that are normal to "self" to do this. In large enough numbers, enough 'stand down' protein is given off by cancer cells that trigger T-cells to stop their attack. Cancer cells are taking advantage of the "self" ability to control T-cell response, just like our otherwise healthy normal cells have the ability to tell T-cells don't attack. A foreign invader can't do that - it doesn't have the cellular machinery of "self" to tell the host T-cells to stop. Cancer cells have the 'self' ability to prevent destruction - they use insider information to benefit and shut down what would otherwise be a T-cell attack. 

 

This is important to understand.

 

As we grow from a single cell - T-cells come later in our development after enough normal cells are around creating a pool of proteins that tell the eventual T-cells to not attack 'self'. This is how the body learns how to not attack itself. Enough normal cells are created in order to have enough critical mass of "normal" that T-cells learn self. Then when a cancer cell (few) emerges, there are not enough of them to have impact on the T-cell to not attack it. The cancer cell is killed. Somehow - cancer develops as a disease because a big enough population of cancer cells gets created at one time before T-cells can respond - there is suddenly enough cancer cells putting out "don't kill me" proteins that tell T-cells (that otherwise might have attacked it) not to attack - the T-cell checkpoints have been activated.

 

Allison's research is exciting because ways are being discovered to either prevent cancer cells (only ) from giving off the stand down command or to prevent T-cells from getting checked in the first place. 

 

Curing cancer lies in our own immune system being able to identify and kill cancer cells without the cancer cells shutting them down. Drugs that help our own bodies do this will lead to cures. Drugs that only kill cancer cells, like our TKI's, do not lead to cures on their own since cancer cells are spontaneously created all of the time (i.e. kill all of the cells is not sufficient new ones spring up). Those of us who do get functionally cured (a small percentage of the overall CML patient population taking TKI's), are probably cured by their own immune system maintaining the attack on cancer once the TKI is removed.  TKI's probably reduced the tumor burden enough to lower the population of CML cells sufficiently to no longer shut down a T-cell attack. 

 

There has to be a monitoring sentry (T-cells) that spots re-emergence of the same cancer. Teaching our body's to know the difference between when to shut down a T-cell attack and when not to is thrilling research. It will probably lead to cures in auto-immune diseases as well.  It is all very exciting.

[Gail's]

So exciting to see researchers heading down the road to immunotherapy. I also believe that a weakened immune system allows cancer cells to grow and take over. If an agent is developed to help T cells recognize cancerous cells, it would have to be extremely good at recognizing just the abnormal cells and not kill off the good guys too. Seems a difficult problem, but glad it's being researched.