New Progresses on Cancer Immunotherapy

1 Blocking the function of special proteins may increase the effectiveness of immunotherapy

Immunotherapy can attack cancer cells by stimulating the patient’s own immune system, which can quickly alleviate the diseases of some cancer patients. This therapy has brought revolutionary changes in the treatment of cancer patients, but in fact it can only treat less than a quarter of patients because tumors can effectively avoid the host’s immune system. Recently, scientists from Washington University School of Medicine and other institutions have discovered that blocking the function of the TREM2 protein may enhance the therapeutic effect of standard immunotherapy drugs, which is expected to completely eliminate tumors. Researcher Marco Colonna said that in essence, they have discovered a new tool that can enhance tumor immunotherapy. The use of antibodies against TREM2 protein alone can reduce the growth of certain tumors. At present, some anti-TREM2 antibodies have entered clinical trials for the treatment of other diseases.

2 Immune cell steroids are expected to help develop new cancer immunotherapies

Recently, scientists from the Institute of Sanger College in the United Kingdom and other institutions have discovered that tumors may enable immune cells to produce immunosuppressive steroids to avoid the host’s immune system. The research was published in Nature Communications. The researchers pointed out that immune T cells from mouse skin and breast tumors can secrete steroids, and inhibiting the production of these steroids can reduce the growth of tumors in mice. Related research results show that removing key steroid-producing genes or using drugs to turn off the expression of this gene can significantly slow the formation or progression of cancer. The researchers said that the steroid signaling pathway may contain potential drug targets, which can help researchers develop new cancer immunotherapies.

3 New potential targets for immunotherapy to treat melanoma have been identified

Scientists from institutions such as the QIMR Berghofer Medical Institute have revealed why some patients with melanoma do not respond well to immunotherapy. Related research results may help researchers develop new targeted therapies for the treatment of potentially fatal cancers. The research was published in Clinical Cancer Research. In this study, researchers found that a special protein called CD155 in human melanoma cells may make skin cancer more difficult to treat with immunotherapy. The researchers revealed the importance of CD155 for the effectiveness of immunotherapy for patients with metastatic melanoma, which has not been found in humans before.

4 Studing the life cycle of exhaustive T cells to develop more effective immunotherapy

Mapping the life cycle of immune cells that have lost their vitality in the fight against cancer allows researchers at the University of Pennsylvania School of Medicine to better understand how future immunotherapy can rejuvenate these cells and help attack diseases. The chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania, Dr. E. John Wherry demonstrated the four key stages of the development of so-called “exhausted” T cells for the first time in a new study and the molecular mechanism of transition between each stage. Past studies have identified different developmental stages of exhaustive T cells, but none of the studies provide a complete picture like this one.

5 Identifying new T cell immunotherapy targets is expected to help develop new therapies against cancer and autoimmune diseases

Recently, scientists from the University of California and other institutions have discovered that CRISRP screening of regulatory T cells may be expected to reveal the regulator of Foxp3 molecules. Foxp3 is one of the key transcription factors that control the development and function of Treg cells (regulatory T cells). This research was published in Nature, entitled “CRISPR screen in regulatory T cells reveals modulators of Foxp3”. Treg cells are the key cells that control the body’s immune response and maintain the body’s balance, as well as an important barrier to the body’s anti-tumor immunity. A comprehensive and in-depth understanding of the pathways that regulate Foxp3 factors may help researchers develop more effective Treg therapies to treat a variety of autoimmune diseases and cancers.

6 The discovery of a new immune brake-EGR4 is expected to help develop new anti-cancer immunotherapies

In a new study, researchers from Temple University’s Lewis-Katz School of Medicine and Fox Chase Cancer Center discovered for the first time that a molecule called EGR4 that plays an important role in male fertility can act as a key brake for immune activation. They also found that removing EGR4 (that is, effectively releasing this key brake) can promote the activation of killer T cells, which infiltrate and attack tumors, thereby enhancing anti-cancer immunity. Related research results were recently published in EMBO Reports. In initial experiments, these researchers found that T cell activation is associated with upregulation of EGR4. They later found that knocking out or eliminating EGR4 from immune cells resulted in a sharp increase in calcium signaling and expansion of the Th1 cell population. Th1 cells respond to the presence of foreign entities including tumor cells, activate killer T cells, and then eliminate invaders.

7 Gasdermin E-mediated pyrolysis is a new anti-cancer immunotherapy

Tumors have found various ways to prevent the immune system from attacking them, and people have responded with cancer immunotherapy. In immunotherapy, inhibitors are mainly used to help the immune system recognize foreign cancer cells. Another method is CAR-T cell therapy, which refers to directly transforming people’s T cells to effectively recognize cancer cells and kill them. However, this method is only suitable for a small number of cancer types, and CAR-T cell therapy has great risks. Researchers have proposed another strategy, which may play a role in more types of cancer. It refers to reactivating a gene called gasdermin E to use immune response to attack cancer cells, but this immune response is suppressed in many cancers. Gasdermin E is a very effective tumor suppressor gene, but in most tumor tissues, it is either not expressed or mutated. When Gasdermin E is reactivated in a tumor, it can turn a’cold’ tumor that the immune system cannot recognize into a’hot’ tumor that the immune system can control.

8 Drawing the first atlas of human thymocytes opens the door to the development of new cancer immunotherapies

In a new study, researchers from research institutions such as Newcastle University in the United Kingdom, the Sanger Institute of the Welkom Foundation, and the University of Ghent in Belgium have mapped out the thymus tissue throughout human life to understand how it develops, and how it produce important immune cells called T cells. In the future, this information may help scientists create artificial thymus and design improved therapeutic T cells. The relevant research results were published in Science. This atlas of the human thymus reveals new cell types and identifies signals that indicate how immature immune cells develop into T cells. Problems in the development of the thymus can lead to defective T cells, which can lead to severe immune deficiencies (such as SCID), making people vulnerable to infections. The thymus also affects T cell regulation, leading to autoimmune diseases such as type 1 diabetes.

9 A new idea that is expected to accelerate the development of cancer immunotherapy is proposed

The ability of tumors to mutate can make them avoid chemotherapy and other therapies. Therefore, in cancer treatment, promoting cancer cells to produce genetic mutations is not a reasonable path for researchers. Recently, scientists from the Mayo Clinic and other institutions used a perverse method to conduct research by analyzing mouse models and human cells. They found that when cell mutations make cancer cells resistant to chemotherapy, it also promotes cancer cells’ sensitivity to immunotherapy. Researcher Dr. Richard Vile said that after studying children’s brain tumor and melanoma models, it was found that high levels of APOBEC3B protein in mice may drive a higher tumor mutation rate. At the same time, high levels of APOBEC3B will also promote the sensitivity of cancer cells to immune checkpoint inhibitors.

10 Blocking VISTA is expected to improve the efficacy of cancer immunotherapy

Researchers from the Geisel School of Medicine in Dartmouth and the University of Minnesota have studied an important target that regulates the immune response in cancer and autoimmune diseases: VISTA (V-domain Ig suppressor of T-cell activation, T cell activation V domain Ig inhibitor). As a regulatory molecule, VISTA prevents T cells in the immune system from being activated by autoantigens (such as antigens in cancer cells). This new study describes how VISTA controls T cell responses, and the results of the study are published in Science. Dr. Noelle and his research team have identified some molecules that the immune system uses to regulate the immune response. Although these molecules usually play a beneficial role, they also limit the strength of the anti-tumor immune response. Turning off these molecular “brakes” that suppress the immune response can treat cancer, and VISTA is one of these molecular brakes that negatively regulate the immune response.