Mechanisms of immune dysfunction in infection and cancer is the focus of our reseach studies.
We have developed a simplified and robust assay to assess SARS-CoV-2 specific T cell immunity in human following COVID-19 infection and/or vaccination (Törnell et al. J Inf Dis 2022). We report long-lasting T cell memory following natural COVID-19 infection (Martner et al. PNAS 2022), and reduced antigen-specific T cell response in vaccinated immunosuppressed patients (Einarsdottir et al. Haematologica 2022, Al-Dury et al- JHEP Rep 2022). We will refine this assay to monitor T cell immunity to seveal other pathogens, including tick-borne encephalitis virus, varicella-zoster virus and hepatitis B virus.
Our group also studies the potential impact of NOX2-derived reactive oxygen species (ROS) for the growth and metastatic spread of malignant cells (Martner et al. J Pathol, 2019). In addition, we address the possibility of targeting NOX2 for therapeutic purposes.
We have developed murine models of NOX2+ myeloid leukemia for mechanistic studies of NOX2 inhibition. Our results indicate that genetic or pharmacologic targeting of NOX2 reduces the expansion of NOX2+ myeloid leukemic cells in vivo (Aydin et al. Oncogene, 2019; Kiffin et al. Front Oncol, 2018).
Additionally, we have developed murine models of solid cancer, including metastasis models and models to evaluate metastasis formation in the context of an inflammatory insult. In several of these models, NOX2+ host myeloid cells infiltrate solid and metastatic tumor tissue and produce immunosuppressive ROS. Our initial results imply that genetic or pharmacological inhibition of NOX2 reduces tumor growth (Grauers Wiktorin et al. Cancer Immunol Immunother, 2019), reduces metastasis formation (Aydin et al. Cancer Immunol Res, 2017) and erases the enhanced metastasis that is associated with surgery-induced inflammation (in manuscript). In addition, animal experiments imply that NOX2-inhibition ameliorates anti-tumor effects of PD-1 pathway immune checkpoint inhibitors (Grauers Wiktorin et al. Cancer Immunol Immunother, 2019).
In parallel with these murine studies, we cooperate with leading hematologists, oncologist and surgeons aiming to validate these findings in patients undergoing immunotherapy. The proposed studies may point towards novel strategies for improved cancer immunotherapy, including inhibition of NOX2 in conjunction with anti-PD1 therapy.