Andreas Lundqvist

Due to their important role to eradicate tumors, natural killer (NK) cells are increasingly utilized in cancer immunotherapy. While the infusion of NK cells shows clinical benefit in hematological malignancies, NK cell therapy has yet to show therapeutic potential in patients with solid tumors. We recently discovered a unique subset of tumor-infiltrating NK cells that exert immune regulatory functions to inhibit anti-tumor T cell responses in solid tumors. Our preliminary results support that these NK cells also play a critical role to orchestrate changes within the tumor microenvironment and to affect epithelial-to-mesenchymal transition (EMT). In this project, we will use in vitro and in vivo models and ex vivo analysis of patient material to address how these NK cells remodel the tumor microenvironment via the crosstalk with myeloid cells, influence the EMT process to promote metastatic dissemination, and interfere with clinical responses to immune checkpoint therapy. In aggregate, we anticipate these studies will support the role of tumor-infiltrating NK cells to suppress local and systemic immune responses and favor tumor progression, metastatic dissemination, and interfere with therapy. Such findings have direct implications to improve therapies based on activating NK cell as well as to implement predictive and prognostic biomarkers in patients with cancer.

Approximately one in three people will be affected by cancer at some point in their life, and in Sweden almost 70,000 people get the disease every year. Therefore, there is a growing need for new treatment methods that aim to prolong the lives of those who have contracted cancer. Advances in cancer research have given new hope to those affected by cancer. In particular, research and treatment in immunotherapy, which relies on the ability of our immune system to fight and destroy cancer cells, has undergone remarkable development in recent years. One cancer that responds to immunotherapy is kidney cancer. Unlike other cancers, it is seen that a certain type of white blood cell, NK cells, affects the course of the disease in patients with kidney cancer. It is therefore important to understand how the activity of NK cells is regulated in patients with kidney cancer. In this project, we use different model systems in a specially adapted laboratory environment to investigate the mechanisms that regulate the activity of NK cells in patients with kidney cancer. We will also investigate how NK cells are affected during treatment with immunotherapy. These studies will provide answers to important questions about how the immune system is regulated in patients with kidney cancer, and will form the basis for developing improved immunotherapy. We also expect to identify markers that can distinguish which patients have a higher chance of being successfully treated with immunotherapy. These findings may lead to patients with disseminated kidney cancer being offered a more effective treatment without serious side effects.

Approximately every third person comes to cancer at some point in their lives, and in Sweden almost 60,000 people fall ill each year. Therefore, there is a growing need for new treatment methods aimed at prolonging the lives of those who have suffered from cancer. Progress in cancer research has given new hope to those affected by cancer. In particular, research and treatment in immunotherapy has undergone a remarkable development in recent years. Immunotherapy is based on the ability of our immune system to fight and destroy cancer cells. Despite promising results, far from all patients are successfully treated with immunotherapy. To understand how the immune system can be activated in patients with cancer, it is important to understand how cancer cells inhibit the immune system. With this knowledge one can better activate the immune system and thereby obtain better treatment results. In this project, we investigate the factors underlying why patients with spread kidney cancer respond to treatment with immunotherapy. In ongoing projects, we have identified two key mechanisms how cancer inhibits the immune system. We now move on and investigate how these mechanisms affect the immune system in patients with kidney cancer. These studies will answer important questions about how the immune system is regulated in patents with kidney cancer, and will be the basis for developing improved immunotherapy treatment. We also expect to identify factors that can distinguish which patients respond to immunotherapy treatment. These findings can lead to patients with spread kidney cancer being offered a more effective treatment without serious side effects.

Cancer is one of the great diseases of our time. Approximately every third person comes to cancer at some point in their lives, and in Sweden almost 60,000 people fall ill each year. Therefore, there is a growing need for new treatment methods aimed at prolonging life and increasing the quality of life for those who have contracted cancer. Progress in cancer research has given new hope to those affected by cancer. In particular, research and treatment in the field of immunotherapy has undergone a remarkable development in recent years. Immunotherapy is based on the ability of our immune system to fight and destroy cancer cells. A tumor mass consists of surrounding support tissue that protects and helps tumor cells to grow and spread. There is clear evidence that this support tissue has an ability to weaken the immune system. Our research has for several years focused on investigating the mechanisms that underlie how the support tissue weakens the immune system. Based on our previous findings, we now proceed and investigate how the immune system can be better activated to withstand these mechanisms and investigate various strategies for breaking down the support tissue. In this way, we can make cancer cells more sensitive to treatment with immunotherapy. These studies will answer important questions about how the immune system is regulated in tumor tissue, and will form the basis for developing improved immunotherapy treatments for patients with cancer. We mainly study patients with kidney cancer and thyroid cancer, but we expect that our results can be applied in most cancer diseases in order to ultimately benefit many patients. Based on our previous experiences, preliminary results, and a large network of partners, we expect the results from these studies to be implemented in clinical trials within the next four years.

Cancer is one of the great diseases of our time. Approximately every third person comes to cancer at some point in their lives, and in Sweden almost 60,000 people fall ill each year. Therefore, there is a growing need for new treatment methods aimed at prolonging life and increasing the quality of life for those who have contracted cancer. Progress in cancer research has given new hope to those affected by cancer. In particular, research and treatment in the field of immunotherapy has undergone a remarkable development in recent years. Immunotherapy is based on the ability of our immune system to fight and destroy cancer cells. A tumor mass consists of surrounding support tissue that protects and helps tumor cells to grow and spread. There is clear evidence that this support tissue has an ability to weaken the immune system. Our research has for several years focused on investigating the mechanisms that underlie how the support tissue weakens the immune system. Based on our previous findings, we now proceed and investigate how the immune system can be better activated to withstand these mechanisms and investigate various strategies for breaking down the support tissue. In this way, we can make cancer cells more sensitive to treatment with immunotherapy. These studies will answer important questions about how the immune system is regulated in tumor tissue, and will form the basis for developing improved immunotherapy treatments for patients with cancer. We mainly study patients with kidney cancer and thyroid cancer, but we expect that our results can be applied in most cancer diseases in order to ultimately benefit many patients. Based on our previous experiences, preliminary results, and a large network of partners, we expect the results from these studies to be implemented in clinical trials within the next four years.

Cancer is one of the great diseases of our time. Approximately every third person comes to cancer at some point in their lives, and in Sweden almost 60,000 people fall ill each year. Therefore, there is a growing need for new treatment methods aimed at prolonging life and increasing the quality of life for those who have contracted cancer. Progress in cancer research has given new hope to those affected by cancer. In particular, research and treatment in the field of immunotherapy has undergone a remarkable development in recent years. Immunotherapy is based on the ability of our immune system to fight and destroy cancer cells. A tumor mass consists of surrounding support tissue that protects and helps tumor cells to grow and spread. There is clear evidence that this support tissue has an ability to weaken the immune system. Our research has for several years focused on investigating the mechanisms that underlie how the support tissue weakens the immune system. Based on our previous findings, we now proceed and investigate how the immune system can be better activated to withstand these mechanisms and investigate various strategies for breaking down the support tissue. In this way, we can make cancer cells more sensitive to treatment with immunotherapy. These studies will answer important questions about how the immune system is regulated in tumor tissue, and will form the basis for developing improved immunotherapy treatments for patients with cancer. We mainly study patients with kidney cancer and thyroid cancer, but we expect that our results can be applied in most cancer diseases in order to ultimately benefit many patients. Based on our previous experiences, preliminary results, and a large network of partners, we expect the results from these studies to be implemented in clinical trials within the next four years.

Cancer often requires many different therapies, such as surgery, radiotherapy and chemotherapy. Despite great advances in cancer research, there are still difficult to treat tumor types. This has justified the search for alternative treatment methods. One example of this is immunotherapy, which activates the immune system against cancer. Research in tumor immunology has led to the availability of approved immunotherapy drugs today. However, the number of patients cured is low. In our research, we try to enhance the effect of immunotherapy. One form of immunotherapy is based on infusion of white blood cells. In this treatment white blood cells are isolated, so-called. T cells and NK cells from patients with cancer. These cells are activated outside the body and then returned to the patient. In order to enhance the effect of immunotherapy, we try to modify T and NK cells so that they can more easily find the tumor and at the same time induce a higher degree of tumor rejection. Immunotherapy can be applied to virtually all types of cancer. In our model systems, we currently evaluate immunotherapy for melanoma, bladder cancer and thyroid cancer. In these projects, tailor-made laboratory methods and animal experiments are used in mice. We expect results from these studies to map out some of the mechanisms that control the immune system in cancer. At the Cancer Center Karolinska, we have a laboratory that is currently used to produce NK and T cells for clinical use. Our long-term goal is to improve immunotherapy with NK and T cells and to develop clinical studies in patients with cancer.