Lars Olaf Cardell

Background: Allergic asthma is driven by T helper (Th2) cells, which expand in response to seasonal allergens and drive inflammation via cytokine release. While the metabolic regulation of T cell function is well studied in general immunology, intracellular glycosylation, especially O-GlcNAcylation, has been largely ignored in allergic disease. This nutrient-sensitive modification, which acts as a metabolic switch, is crucial for T cell activation and cytokine production, but its role in asthma is unknown. Our pilot data in allergic rhinitis patients show increased T cell O-GlcNAcylation after pollen season, indicating that allergen exposure may imprint lasting metabolic changes relevant for asthma pathogenesis. Objective: We hypothesize that allergen exposure increases O-GlcNAcylation in pathogenic T cells and neutrophils, promoting inflammation and bronchial hyperresponsiveness in allergic asthma. Work Plan: The project is organized into five integrated work packages: 1. WP1 quantifies O-GlcNAcylation in peripheral T cells in and out of pollen season (flow cytometry). 2. WP2 assesses how neutrophil extracellular traps (NETs) and bronchial tissue O-GlcNAcylation influence airway reactivity (ex vivo organ bath). 3. WP3 examines if expanded allergen-specific TCR clones exhibit elevated O-GlcNAc levels (TCR sequencing). 4. WP4 localizes O-GlcNAc-modified T cells in inflamed airways (immunohistochemistry). 5. WP5 investigates how pharmacologically altering O-GlcNAcylation impacts cytokine production in patient-derived T cells (in vitro assays). Significance: This is the first study to explore O-GlcNAcylation in allergic asthma. It will uncover how metabolism-linked protein glycosylation regulates T cell pathogenicity and NET-driven airway dysfunction. The findings could pave the way for new biomarkers (O-GlcNAchigh T cells), stratified treatments (based on TCR-metabolic profiles), and novel therapeutics targeting metabolic-inflammation pathways. This may offer new treatment options for patients with severe and therapy-resistant asthma.

Background: Despite aggressive surgery coupled with radiation/chemoradiation, the 5-year overall survival rate of oral squamous cell carcinoma (OSCC) has stagnated at 50% for decades. While cancer immunotherapy holds promise, OSCC patients typically experience only modest enhancements compared to other cancer types. Advancing immunotherapies requires a deeper understanding of cancer immunity mechanisms. Insights into neutrophil immunity, with their potential to influence pro- and anti-cancer responses, particularly within tumor-draining lymph nodes (TDLNs), remain limited.Goal: To dissect the immunomodulatory roles of neutrophils in TDLNs across various stages of OSCC and characterize their potential as facilitators of metastasis within these nodes. The project has 4 aims that synergistically build upon one another.Methods: Several techniques, including single-cell sequencing, flow cytometry, and spatial transcriptomics, will be deployed to characterize fresh samples of OSCC tumors, TDLNs, and non-TDLNs, alongside lymph nodes from non-cancer patients. Boyden chambers, in conjunction with an orthotopic xenograft model, will be utilized to investigate the involvement of tumor-associated neutrophils in cancer dissemination to TDLNs.Clinical Implications: A successful outcome has the potential to catalyze the development of novel strategies aimed at bolstering immune responses against cancer, thereby potentially enhancing the effectiveness of existing cancer immunotherapies.

Despite use of standard of care medication most patients with allergic rhinitis (AR) are generally unsatisfied with their quality of life. Allergen-specific immunotherapy (AIT) can improve this but only 5% of the eligible patients receive and complete the required three years of treatment. This mainly due to problems fulfilling the necessary hospital visits every 6 weeks for subcutis injections (SCIT) or poor compliance taking daily tablets at home (SLIT).Intralymphatic AIT (ILIT) conjure a novel route of delivery with shorter duration and good compliance (3 injections over 8 weeks). Our previous studies have demonstrated that ILIT is safe with a sustained ability to reduce symptoms and medication during the pollen season. No studies have compared ILIT with traditional AIT. A recent study has shown that oral vitamin D (vitD) given in parallel to SLIT improves the symptom reduction.Our aim is to investigate if supplementation of vitD in parallel with ILIT can further improve the efficacy. We will also, for the first time, compare ILIT with SLIT.The study will run over four years and include 360 patients with grass pollen induced AR. 240 of them will be treated with ILIT and 120 will receive SLIT.  The former group will be given an im bolus injection of vitD3 or placebo before the first ILIT injection.A successful outcome will give a more easily accessible AIT protocol with high efficacy. It will also save money for the society and increase the quality of life for the patients.

Every year, 650 people in Sweden fall ill with head and neck cancer. If these tumors are detected in time, they can usually be treated successfully. In 1/3 of the cases, however, the tumor is spread already at diagnosis, which leads to poorer survival. Improved diagnostics could therefore lead to a better treatment outcome. A new form of immunological treatment for cancer (check-point blockade) has recently been awarded the Nobel Prize. The problem, however, is that only 20% of the patients treated respond to this type of therapy. Work to find markers for which patients will respond, as well as new forms of immunological intervention, is therefore underway. The research program consists of five partially integrated sub-projects and focuses on the importance of the lymph nodes for diagnosis and treatment. The work is carried out transnationally, ie in the form of a close collaboration between clinic and laboratory. Our preliminary results show that patients who have a weak immune response in their lymph nodes have a higher risk of cancer recurrence and premature death. Our data also show that immunological lymph node activity is a better prognostic marker than those that have emerged so far in studies of both blood and the tumor itself. Our overall goal is to improve both diagnostics and recurrence prognosis based on our gland findings. In the long run, we also hope to be able to develop ways to strengthen the body's own immune system so that tumors can be forced into regression and the risk of recurrence is reduced. This work is based on the patients who today are judged to have the worst prognosis. By analyzing the immune system's reaction to tumor cells, I hope to be able to offer a more individualized immunological treatment where traditional treatment does not work.

Every year, 650 people in Sweden fall ill with head and neck cancer. If these tumors are detected in time, they can usually be treated successfully. In 1/3 of the cases, however, the tumor is spread already at diagnosis, which leads to poorer survival. Improved diagnostics could therefore lead to a better treatment outcome. A new form of immunological treatment for cancer (check-point blockade) has recently been awarded the Nobel Prize. The problem, however, is that only 20% of the patients treated respond to this type of therapy. Work to find markers for which patients will respond, as well as new forms of immunological intervention, is therefore underway. The research program consists of five partially integrated sub-projects and focuses on the importance of the lymph nodes for diagnosis and treatment. The work is carried out transnationally, ie in the form of a close collaboration between clinic and laboratory. Our preliminary results show that patients who have a weak immune response in their lymph nodes have a higher risk of cancer recurrence and premature death. Our data also show that immunological lymph node activity is a better prognostic marker than those that have emerged so far in studies of both blood and the tumor itself. Our overall goal is to improve both diagnostics and recurrence prognosis based on our gland findings. In the long run, we also hope to be able to develop ways to strengthen the body's own immune system so that tumors can be forced into regression and the risk of recurrence is reduced. This work is based on the patients who today are judged to have the worst prognosis. By analyzing the immune system's reaction to tumor cells, I hope to be able to offer a more individualized immunological treatment where traditional treatment does not work.

The incidence of cancer in the tongue / throat almonds has increased in Sweden in recent years and about 650 people fall ill each year, the increase being most apparent in younger (<40 years) patients. The tumors can be successfully treated if detected in time. In more than one third of the cases, the tumor has spread already at the first visit. The treatment is controlled by the tumor's spread and the diagnosis is important, where the cornerstone is microscopic examination of surgical lymph nodes. This requires time, resources and highly trained staff. Tumors that are not detected lead to recurrence of the cancer, are difficult to treat and lead to severe disability or death. We work with a method for finding cancer cells in tissue samples from patients with squamous cell carcinoma of the tongue and oral cavity. We are currently developing a so-called flow cytometry-based method for finding small lymph node metastases. The method is more automated than regular microscopy and allows rapid examination of larger amounts of material per patient than today. We also study the immune system's ability to fight these tumor cells. The goal is to find ways to strengthen the immune system so that the body can have better defense against the cancer. The goal is that by developing new and improved analysis methods, a larger proportion of small metastases will be found than at the same time as cost efficiency is improved in the clinic. We believe that this opens the way for a more individualized therapy where over-treatment with unnecessarily severe residual conditions can be avoided. The last part of the project aims to create a basis for new immunological treatment options to use when traditional treatment does not work.

The incidence of cancer in the tongue / throat almonds has increased in Sweden in recent years and about 650 people fall ill each year, the increase being most apparent in younger (<40 years) patients. The tumors can be successfully treated if detected in time. In more than one third of the cases, the tumor has spread already at the first visit. The treatment is controlled by the tumor's spread and the diagnosis is important, where the cornerstone is microscopic examination of surgical lymph nodes. This requires time, resources and highly trained staff. Tumors that are not detected lead to recurrence of the cancer, are difficult to treat and lead to severe disability or death. We work with a method for finding cancer cells in tissue samples from patients with squamous cell carcinoma of the tongue and oral cavity. We are currently developing a so-called flow cytometry-based method for finding small lymph node metastases. The method is more automated than regular microscopy and allows rapid examination of larger amounts of material per patient than today. We also study the immune system's ability to fight these tumor cells. The goal is to find ways to strengthen the immune system so that the body can have better defense against the cancer. The goal is that by developing new and improved analysis methods, a larger proportion of small metastases will be found than at the same time as cost efficiency is improved in the clinic. We believe that this opens the way for a more individualized therapy where over-treatment with unnecessarily severe residual conditions can be avoided. The last part of the project aims to create a basis for new immunological treatment options to use when traditional treatment does not work.

The incidence of cancer in the tongue / throat almonds has increased in Sweden in recent years and about 650 people fall ill each year, the increase being most apparent in younger (<40 years) patients. The tumors can be successfully treated if detected in time. In more than one third of the cases, the tumor has spread already at the first visit. The treatment is controlled by the tumor's spread and the diagnosis is important, where the cornerstone is microscopic examination of surgical lymph nodes. This requires time, resources and highly trained staff. Tumors that are not detected lead to recurrence of the cancer, are difficult to treat and lead to severe disability or death. We work with a method for finding cancer cells in tissue samples from patients with squamous cell carcinoma of the tongue and oral cavity. We are currently developing a so-called flow cytometry-based method for finding small lymph node metastases. The method is more automated than regular microscopy and allows rapid examination of larger amounts of material per patient than today. We also study the immune system's ability to fight these tumor cells. The goal is to find ways to strengthen the immune system so that the body can have better defense against the cancer. The goal is that by developing new and improved analysis methods, a larger proportion of small metastases will be found than at the same time as cost efficiency is improved in the clinic. We believe that this opens the way for a more individualized therapy where over-treatment with unnecessarily severe residual conditions can be avoided. The last part of the project aims to create a basis for new immunological treatment options to use when traditional treatment does not work.