In 2011, ipilimumab was approved for the treatment of melanoma, marking the beginning of the tumor immunotherapy revolution, in 2013, tumor immunotherapy was selected as the first of Science's top ten scientific and technological breakthroughs, and the 2018 Nobel Prize in Physiology or Medicine was awarded to American scientist James Allison and Japanese scientist Yu Honjo in recognition of their contributions to "discovering negative immunomodulatory therapies for the treatment of cancer".
Xinhua News Agency photo, October 1, 2018 (1) U.S. and Japanese scientists share the 2018 Nobel Prize in Physiology or Medicine
What is the sacredness of tumor immunotherapy that is developing so rapidly?
On the occasion of the "World Immunization Booster Day" on December 15, Professor Su Shicheng of the Breast Cancer Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University will take you to unveil the mystery of tumor immunity and interpret the new dawn of cancer patients.
Su Shicheng, chief physician and researcher of Breast Cancer Center, is currently a member of the Party Committee and assistant to the president of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, deputy director of Breast Cancer Center, director of Yixian Breast Laparoscopy Center, director of Shuhua Breast Cancer Research Center, and director of Biotherapy Technology Center.
Q: Has immunotherapy been listed as a cancer treatment technology?
Su Shicheng: Yes! Immunotherapy is another major tumor treatment technology after surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy, which is different from the direct killing and killing of cancer cells by traditional treatments such as surgery, chemotherapy and radiotherapy, which mainly kills cancer cells by activating the body's own immune system.
Q: What is the principle of tumor immunotherapy?
Su Shicheng: The immune system is a line of defense to guard human health, immune cells are "patrolling soldiers", normal human body in the process of cell replication will also produce a small number of malignant cells, but immune cells can timely recognize and remove these small amounts of malignant cells. When immunity declines, the surviving malignant cells continue to evolve and camouflage, resulting in immune cells unable to recognize in time, malignant cells eventually develop into tumor tissues visible to the naked eye, and cancer occurs.
The mechanism of action of tumor immunotherapy is very simple, taking the main checkpoint inhibitor PD1/PD-L1 antibody widely used in breast cancer immunotherapy as an example:
(1) T cells use detection equipment to verify cell identity: human cells carry "PD-L1 protection card", and T cells carry "PD-1 detection equipment". T cells are the elite troops of the immune system soldiers, the lethality is amazing, the first step in the task is to verify the identity, that is, the T cells identify PD-L1 through the "PD-1 detection equipment", receive protective signals, and will not attack their own cells. Therefore, PD1/PD-L1 is also known as "immune checkpoint".
(2) Tumor cell camouflage: In evolution, cunning tumor cells learned to camouflage and also carried the "PD-L1 protection card", so that T cells mistakenly thought they were their own cells and did not kill.
(3) Blocking the detection equipment of T cells: The PD-1 antibody currently used in clinical application mainly acts on T cells, which is equivalent to blocking the detection equipment of T cells, and the PD-L1 antibody confiscates the "PD-L1 protection card" of tumor cells, so that its identity is exposed.
(4) T cells discover tumor cells through other pathways: T cells identify cells through other pathways, identify tumor cells in time and solve them early.
Q: How effective is immune therapy?
Su Shicheng: Compared with traditional treatment, immunotherapy has three main advantages: first, it can refer to immune memory, the "survival tailing effect" is significant, and patients with effective immunotherapy have a great chance of high-quality long-term survival; Second, it can treat advanced cancer that has been widely metastasized, especially for cancer patients who have failed all standard therapies, and can still achieve good results; Third, immunotherapy is broad-spectrum, which can treat a variety of different cancers and make the same treatment of different diseases a reality.
Q: Are all patients suitable for immunotherapy?
Su Shicheng: No! Immunotherapy relies on the body's own immune system to attack tumors, so it is especially important to evaluate the patient's condition before use. This is why immuno-oncology therapy, despite being one of the fastest growing cancer treatments at present, currently only 20-30% of patients benefit!
Q: What are the important evaluation indicators suitable for immunotherapy?
Su Shicheng: Tumor immunotyping is an important evaluation index.
Immune cells need to enter the tumor to recognize and attack tumor cells, so tumor cells usually set up multiple barriers to prevent immune cell infiltration. According to the degree of immune cell infiltration of the tumor, tumors can now be divided into three immunophenotypes: inflammatory (immune cells inside the tumor), immunoexclusionary (immune cells outside the tumor), and immune desert (lack of immune cells). Among them, inflammatory tumors can produce an effective immune response and are most sensitive to immune checkpoint inhibitor therapy, and these patients tend to have a better survival prognosis.
Of course, relying on tumor immunotyping alone is obviously not enough, so basic and clinical research are committed to finding new indicators so that more tumor patients can be suitable for immunotherapy.
Q: Will I resist after receiving immunotherapy?
Su Shicheng: Like other treatments, tumor immunotherapy may also develop drug resistance! However, our team isolated a CD16+ fibroblast from tumor specimens from breast cancer patients and found that it plays a key role in tumor connective tissue proliferation, hindering the delivery of trastuzumab and its drug in combination with chemotherapy in tumor tissue, and by targeting its acting molecules, this resistance can be reversed!
In fact, how to overcome immunotherapy resistance has always been a major topic, and many basic studies are trying to find ways to solve it, and we are still working hard!
Q: Is monotherapy useful for immunotherapy?
Su Shicheng: Taking breast cancer as an example, breast cancer immunotherapy monotherapy has limited efficacy, whether it is early or advanced breast cancer, the efficacy rate of PD-1/PD-L1 immune checkpoint inhibitor monotherapy is low. At present, more combination therapy strategies are explored, such as immunity + chemotherapy, immune + anti-angiogenic therapy, and immune + targeted therapy. With the continuous improvement of diagnosis and treatment technology, breast cancer has become one of the most effective tumors, especially in recent years, with the blessing of immunotherapy, the treatment effect is more significant.
Moreover, the immunotherapies currently available are only the tip of the iceberg of potential immunotherapy strategies. One day, we can stop talking about cancer discoloration, and immunotherapy may be the way to break the game!
Writing; Nandu reporter Wang Daobin correspondent Liu Wenqin Weng Xiaoqi