Several misunderstandings about tumor immunotherapy that you must understand

Immunotherapy has been a hot topic in cancer treatment in recent years. Immunotherapy fights tumors by enhancing the body's immune function. In China, PD-1/PD-L1 immunotherapy has become one of the important means of cancer treatment. At present, there are two main immune checkpoint inhibitors in clinical practice, namely PD-1 inhibitors and CTLA-4 inhibitors. PD-1/PD-L1 inhibitors mainly affect the proliferation, differentiation and death of tumor cells by regulating immune cells, thereby achieving anti-tumor effects. The main function of this therapy is to block the PD-1/PD-L1 pathway, enabling the human immune system to recognize cancer cells and attack them. CTLA-4 inhibitors are a type of drug that directly acts on T cell surface receptors, blocking the binding of PD-L1 on T cells to their receptors, which leads to the pathway for T cells to recognize tumor cells, thereby achieving anti-tumor effects. Since this therapy has achieved very good results in clinical trials, there are currently many related reports and clinical trials in progress.

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1. Is immunotherapy a panacea?

First of all, we must make it clear that immunotherapy is not a panacea. At present, the two immune checkpoint inhibitors available in China are only for patients with advanced cancer. For example, in China, the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) is immune checkpoint inhibitors + chemotherapy; while the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) is immune checkpoint inhibitors + chemotherapy. For patients who fail the first-line standard treatment, combined treatment can currently be used to improve the efficacy. The American Cancer Society (AACR) guidelines stated: "In a clinical trial, the objective response rate of patients with advanced NSCLC was only 14.2% when PD-1 inhibitors were used alone; while the objective response rate was as high as 37.3% when PD-1 inhibitors were combined with chemotherapy." But this does not mean that patients only need to receive one immunotherapy to get better treatment results. Because tumor cells are highly heterogeneous, different types of tumors will respond differently to the same immunotherapy. For example, melanoma is most sensitive to immunotherapy; lung cancer is most sensitive to PD-1/PD-L1 inhibitors; renal cancer is most sensitive to CTLA-4 inhibitors; nasopharyngeal carcinoma is most sensitive to PD-1 inhibitors... Therefore, if patients are not sure whether they will respond to which immunotherapy, they need to consider different treatment options to obtain better treatment effects.

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1. Immunotherapy is not effective?

Although immunotherapy has been developed for nearly ten years, there are still many patients who cannot benefit from immunotherapy in clinical practice. The main reason is that some patients have low or missing autoimmune function, which makes the immune system unable to work normally, resulting in patients being unable to benefit from immunotherapy. Other patients have other diseases, such as diabetes, hypertension, etc., which lead to impaired or reduced immune function, thus affecting the effect of immunotherapy. At present, a large number of studies have confirmed that low or missing autoimmune function in cancer patients is one of the main factors affecting the effect of immunotherapy. Therefore, for cancer patients with low or missing autoimmune function, clinicians need to first understand their physical condition, and then develop individualized treatment plans based on specific circumstances. Only in this way can the treatment effect be truly improved and the quality of life of patients can be improved.
( II ) Tumors can mutate, so immunotherapy is ineffective?

Tumor mutations pose challenges to immunotherapy, but they are not insurmountable. There is evidence that tumor cells resist immunotherapy by regulating their mutated genes. Mutations in tumor cells can be observed in up to 60% of patients receiving immunotherapy, but only a small number of patients will have mutations. Before or after immunotherapy, patients may have some minor genetic changes, and these minor genetic changes may help patients resist immunotherapy. However, not all mutations can become effective immunotherapy targets. Mutations detected before or after immunotherapy are mainly divided into two categories: one is mutations caused by the tumor cells themselves, which cannot cause an immune response in tumor cells; the other is new mutations caused by other reasons, which are called "pathological mutations."

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2. Is immunotherapy only suitable for advanced cancer?

1. Immunotherapy is effective and can bring many cancer patients back to life

According to statistics, in 2018, there were 3.804 million new cancer cases and 1.991 million deaths in my country, with an incidence and mortality rate of 3.63/100,000 and 2.88/100,000, respectively, both exceeding the world average. Take lung cancer as an example. According to the "2018 China Cancer Registry Annual Report" released by the National Cancer Center of China, the number of lung cancer cases and deaths in my country accounted for 53% and 45% of the world's total, respectively. Especially in China, lung cancer has become the leading cause of death from malignant tumors. Since the early symptoms of lung cancer are not obvious, most of them are already in the middle and late stages when diagnosed, and the efficacy of conventional treatment methods is not ideal. However, in recent years, with the advancement of immunotherapy technology and continuous breakthroughs in drug research and development, as well as the development of more and more clinical studies, many patients with advanced lung cancer have regained survival benefits. In particular, the clinical application of immune checkpoint inhibitors has greatly improved the quality of life of patients and prolonged their survival time.
( II ) Immunotherapy also has "side effects", patients need to pay attention

Although immunotherapy can benefit cancer patients, it also has many adverse reactions, such as:
1. Symptoms such as fatigue, weakness, loss of appetite, nausea, and vomiting may occur.
2. Allergic skin reactions may occur, such as rash, urticaria, etc.
3. Fever and infection may occur, especially within 2 weeks of immunotherapy.
4. Patients with impaired immune systems may experience lymphocytopenia after immunotherapy and need to strengthen physical exercise.
5. During immunotherapy, avoid contact with radioactive substances, such as X-rays and gamma rays.
6. During immunotherapy, radiotherapy should be avoided as much as possible before and during immunotherapy.
7. For patients with hypertension, diabetes and other serious underlying diseases, they need to be fully evaluated before using immunotherapy to decide whether they can receive immunotherapy.

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3. Can immunotherapy completely cure cancer?

Immunotherapy can treat many types of cancer, but not all cancers can be treated with immunotherapy. Clinically, except for blood tumors, most solid tumors are unlikely to be cured by immunotherapy. For example, melanoma is a type of tumor that is very sensitive to traditional therapies, but the cure rate of this disease is very low. In contrast, the cure rate of blood tumors and some solid tumors (such as pancreatic cancer and renal cell carcinoma) will be higher. Globally, the 5-year survival rate of melanoma is only about 1%. In contrast, the 5-year survival rate of melanoma in other types of tumors is higher, such as the 5-year survival rate of non-small cell lung cancer can reach 40%-50%, and the 5-year survival rate of prostate cancer patients can reach 60%-70%. Therefore, for patients with advanced melanoma, if complete remission or objective remission is not achieved through immunotherapy, tumor recurrence or progression cannot be ruled out. Therefore, tumor markers and imaging examinations need to be performed regularly during treatment to monitor tumor progression. If patients have symptoms of tumor recurrence or metastasis, immunotherapy regimens need to be re-evaluated in a timely manner. For patients whose cancer cannot be cured by immunotherapy, they can also receive higher-level cancer treatment if they have sufficient financial resources and options to undergo immunotherapy.

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At present, clinical studies on different indications are being conducted both at home and abroad, but there are still some differences between China and foreign countries. For example, in the selection of indications, some patients abroad only need to use one immunotherapy to achieve the treatment effect; while in China, some patients need to receive multiple treatment plans to achieve better treatment effects. Therefore, how to choose the appropriate treatment plan and how to reasonably combine various treatment plans are issues that every cancer patient and oncologist needs to face.