Under normal circumstances, the immune system can recognize and eliminate tumor cells in the human body, but in order to survive and grow, tumor cells use different strategies to suppress the body's immune system and fail to kill tumor cells normally, and the above characteristics of tumor cells are called immune escape.
Tumor immune intervention is an intervention method that restores the body's normal anti-tumor immune response by restarting and maintaining the tumor-immune cycle, so as to control and eliminate tumors.
It is often seen that similar questions are asked: should the immune cell intervention method be used early, or should it be used as a last resort? This question was difficult to answer before, but with the longer and longer follow-up time and more data, the answer has become clear: "If possible, the immune cell intervention method should not be left to the end, and it is better to use it early!"
01
Why is it better to intervene as early as possible?
The principle of immune intervention determines that the sooner the immune intervention, the better!
Traditional treatment methods usually directly target cancer cells, such as surgery to directly remove the primary lesion, chemoradiotherapy to directly kill cancer cells, targeted drugs to block the gene mutation pathway of cancer cells, and so on. But immune interventions, unlike any of them, kill cancer cells by uninhibiting them or activating the immune cells themselves.
Immune intervention has "long-term effect", which is called "survival tailing effect" in technical terms, that is, once the immune intervention is effective, it will continue to take effect, so that patients can obtain long-term survival benefits, which is closely related to how many years the immune intervention can live.
Whether it is a short-term killing of cancer cells or long-term control of tumor recurrence, a healthy immune system is necessary for immune intervention to be effective.
02
When is the immune system healthier?
Of course, the sooner the better.
Many anti-cancer treatments, especially high-dose chemotherapy, have a suppressive effect on the immune system. Many patients' immune cells are already in a poor state in the late stage of treatment, and it is difficult to be activated by immune drugs, and the effect is naturally not good.
A large body of data suggests that patients benefit more from immune interventions.
In 2017, JAMA ONC published a classic article, through the big data analysis of 25 clinical trials and more than 20,000 patients in non-small cell lung cancer, it was found that the survival curves of patients participating in immune intervention and targeted intervention were very different.
In the targeted therapy part of the figure above - the experimental group (blue): the targeted drug is used first, and then the other drug is used after failure, and the control group (orange): the other drug is used first, and then the targeted drug is used after failure.
As can be seen from the figure, the survival curves of the two groups of targeted therapy are very similar, which indicates that the impact of targeted drugs on survival is similar whether they are used first or later.
But immune drugs are a different story entirely.
It can be seen that the overall survival of the immunotherapy test group (first with immune drugs, and then with other drugs after failure) was significantly higher than that in the control group (with other drugs first, and then with immune drugs after failure), and the overall mortality risk of patients was reduced by more than 30%.
This proves that immunotherapy and targeted drugs are very different, and there is a gap between the effect of first use and later use, and the survival period of early use of immune drugs will be better.
The review, published in the international journal "Front Immunol", revealed that the function of the immune system will be damaged after surgery, and the use of radiotherapy and chemotherapy also has a suppressive effect on the immune system, reducing the number of immune cells and tumoricidal activity, which is also the reason why patients are often weak after receiving conventional treatment.
03
The better the patient's status, the better the immune intervention
The commonly used clinical evaluation system for patients' health status is called ECOG PS (ECOG Physical Status Scoring Scale), and the smaller the score, the better the physical state.
Score 0 - Mobility is completely normal, with no difference from pre-onset.
Band 1 - Able to move freely and engage in light physical activities, including general household chores or office work, but not heavy physical activities.
2 points - Able to move around freely and take care of themselves, but have lost the ability to work, and can get up and move at least half of the day.
3 points - can only partially take care of themselves, and spend more than half of the day in bed or in a wheelchair.
4 points - bedridden and unable to take care of himself.
5 points - death.
Many clinical trials have found that patients who are in good health respond better to immune medications. For example, in 2016, the results of the clinical trial of drug O (codenamed CheckMate153) presented at the World Conference on Lung Cancer showed that patients with a PS score of 0~1 benefited much better from immunotherapy than patients with a PS score of 2.
Generally speaking, the later the patient's physical condition becomes, especially if drugs such as chemotherapy are used. Patients on first-line therapy are often in much worse condition than first- or second-line therapy.
These data also support the early use of immune drugs, don't wait until the end, your body is so bad that you can't think about "coming back to life".
In short, immune cells are not an intervention that needs to be considered at the end of life, and early use is more effective.