【Immune awakening】
台大醫院某教授來做有關 cancer immunotherapy 精彩生動的演講
究竟，T cell 如何被壞巫婆(腫瘤細胞)變成睡美人，而我們又該如何當王子去叫醒睡美人呢?
What the immune system does?
Immune cells and the substances they make travel through your body to protect it from germs that cause infections.
They also help protect you from cancer in some ways.
首先，先瞭解身體內正常免疫細胞在體內是警衛的角色，會在全身巡邏，去抓取是否有像細菌或病毒等外來物的入侵並加以消滅
其中包含癌細胞也會被判定是外來物。
Clearly there are limits on the immune system’s ability to fight cancer on its own, because many people with healthy immune systems still develop cancer.
Sometimes the immune system doesn’t see the cancer cells as foreign because the cells aren’t different enough from normal cells.
Sometimes the immune system recognizes the cancer cells, but the response might not be strong enough to destroy the cancer.
Cancer cells themselves can also give off substances that keep the immune system in check.
但有時候我們的警衛，無法辨識癌細胞，因為它長的和一般細胞差異不大，又或者癌細胞將我們的警衛給催眠成睡美人，使它昏睡無法執行任務
cancer immnoediting
In the first phase of elimination, cells and molecules of innate and adaptive immunity, which comprise the cancer immunosurveillance network, may eradicate the developing tumor and protect the host from tumor formation.
However, if this process is not successful, the tumor cells may enter the equilibrium phase where they may be either maintained chronically or immunologically sculpted by immune “editors” to produce new populations of tumor variants. These variants may eventually evade the immune system by a variety of mechanisms and become clinically detectable in the escape phase.
在正常細胞突變成癌細胞之初期，若我們免疫細胞無法將其殺死，那它將變成不死之身開始茁壯
What is cancer immunotherapy?
- Stimulating your own immune system to work harder or smarter to attack cancer cells
- Giving you immune system components, such as man-made immune system proteins
免疫治療又簡易的分為兩大類
主動免疫：治療就是一個喚醒自身的免疫細胞去打爆癌細胞的概念
被動免疫：將對抗某特定癌種的抗體直接注射進入患者體內，壓制癌細胞的轉移或是對於癌細胞產生毒殺作用以達到治療效果。
這些特定抗體可以從具有免疫力的個體血液中純化，或者經由生化合成的方式製造。
What's new in cancer immunotherapy research?
這裡就只提演講中教授有說到的兩個
chimeric antigen receptor (CAR) T-cell therapy
This is a promising new way to get immune cells called T cells to fight cancer. For this technique, T cells are removed from the patient’s blood and genetically altered in the lab to have specific antigen receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors will attach to proteins on the surface of cancer cells. The T cells are then multiplied in the lab and infused back into the patient’s blood, where they can now seek out the cancer cells and launch a precise immune attack against them.
This technique has shown very encouraging results in early clinical trials against some advanced, hard-to-treat types of leukemias and lymphomas. In many people the cancer could no longer be detected after treatment, although it’s not yet clear if these people have been cured.
Immune checkpoint inhibitors to treat cancer
An important part of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells while leaving the normal cells alone. To do this, it uses “checkpoints” – molecules on certain immune cells that need to be activated (or inactivated) to start an immune response.
Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints hold a lot of promise as cancer treatments.
在某些免疫細胞(像T cell) 會有checkpoint來判定他接觸到的東西是否屬於外來物，是的話就予以清除。
而有些腫瘤細胞會催眠這個checkpoint，讓免疫細胞以為是自己人，腫瘤細胞進而壯大
target PD-1 or PD-L1
PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them evade immune attack.
Monoclonal antibody treatments that target either PD-1 or PD-L1 can boost the immune response against cancer cells and have shown a great deal of promise in treating certain cancers. Examples of treatments that target PD-1 include:
針對T-cell 上有的PD-1 或 腫瘤細胞上的PDL-1將其阻斷，讓腫瘤細胞不能躲過T cell的追殺
晨會心得：
1.癌細胞可以利用一些突觸來催眠我們的T cell它是自已人，如何把T cell打醒是一個重點。那醒來後的T ecll又可以從質和量上面去看，夠多就可以用量來取勝殺死癌細胞，或以質來取勝將其改裝成葉問版本的Tcell，用一個打十個癌細胞，當然最好的是可以有量又有值，但如果要兩者取其一的話，值絕對比量來的重要。
2.免疫治療並非所有的癌症都適用，
3.目前治療成本很高
P.S. 若有任何醫學知識上的錯誤，懇請指正和討論，謝謝。
Ref:
1.American cancer society
2.Dunn et al., Immunity (2004) 21, 137-148
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