探索癌症

Here are some of the things I've learned over the past two years.

CTLA-4 pathway blocks the immune system from starting an immune response against cancer. How tumor employ this mechanism to block anti tumor response is still not completely known. What the scientists do know is when the dendritic cells present tumor antigens to an naive T-cell (a T cell which never been activated), it fails to activate the T-cell.

PD-1 is more direct. Most cancer types use this mechanism to fend of T cell attack. PD-1 is a receptor on the T cells. It stands for Programmed Death-1. When attached by PDL1, the T cell become deactivated, and will die over a period of time. When cancer cells are under T cells attack, dying cancer cells secret substances to alert cancer cells nearby. These cancer cells will respond to the signal by presenting PDL1 on their cell surface. When T cells attack these cancer cells, T cells will become deactived and die gradually. This is why T cell therapy, DC cell therapy and cancer vaccine maybe only effective for a short time.

My observation is anti PD1 is effective in preventing the disease from spreading.
This is logical because T cells are based in lymph nodes and lymph nodes are body's check point for intruders**. Lymph system are interconnected to blood vessel system to form a complex network. All substances (virus, bacteria, cancer cells) flowing in the blood vessel are subject to examination of the T-cells (a white blood cell). In my opinion, it is easier to eliminate free flowing cancer cells. And this observation is back by medical data. In a recent Nivolumab clinical trial, Hodgkin lymphoma achieved a high response rate 87% (20/23).

Solid tumors are harder to attack. Still using anti PD1 to treat various cancers, we still see an average of 20% response rate, which is remarkable in my opinion.

Solid tumors are cluster of cancer cells. 1 cm of tumor packed with 1 billion cancer cells.
Solid tumors have several defense mechanism to fend off immune system attack.
1) thick wall called vasculature.
2) regulatory T cells and Dentritic cells, macrophage, MSDC in the tumor micro environment, which can turn off anti tumor immune response. (All of above use PDL1 to turn off immune response, that is why anti PD1 is so critical in the fight with cancer).
3) PDL1 on cancer cells.

Even armed with anti PD1, a T cell works on one cancer cell at a time. Patients who previously treated with chemo therapy generally have weaker anti tumor immune response. These could mean less number of cytotoxic T cells. If tumor grows faster than the T cells are able to eliminate them, the tumor may appear to be growing. Thus, anti PD1 works best when combined with radiotherapy or target therapy or even chemotherapy. Use traditional therapy to destroy as much tumors as possible, then start on anti PD1 to chase after remaining cancer population.

**Many cancer patients have swollen lymph nodes, which indicates their immune system detected tumor cells and have activated immune response. These patients should try Anti PD1. On the other hand, if the cancer cells can sneak pass lymph nodes without being recognized, the immune system may not be able to recognize the cancer cells, thus, Anti PD1 may not be effective. The rule of thumb is the more mutation the cancer cells have, the easier the immune system is able to recognize and eliminate them.