Katharina von Ahn's research while affiliated with Universität Heidelberg and other places

Publications (9)

Article
Full-text available
Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. How...
Article
Full-text available
Interferon-α (IFNα) has one of the longest histories of use amongst cytokines in clinical oncology and has been applied for the treatment of many types of cancers. Due to its immune-activating properties, IFNα is also an attractive candidate for combinatory anti-cancer therapies. Despite its extensive use in animal tumor models as well as in severa...
Article
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. PDAC cells activate tumor-specific immune responses but simultaneously trigger a strong immunosuppression. We showed that PDAC cells produce high amount of chronic inflammatory mediators and PDAC tumors build an immunosuppressive cytokine milieu, which cor...
Article
B7-H1 regulatory protein, a member of the B7-H family, plays a crucial role in the modulation of immune response in healthy steady-state conditions as well as in different pathologies. B7-H1 knockout mice represent an important model to elucidate further molecular and cellular mechanisms involved, among others, in autoimmunity development and cance...
Article
Full-text available
Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combina...
Article
Phosphodiesterase 5 (PDE5) is a pharmacological target in erectile dysfunction, pulmonary hypertension and in other indications. In tumor-bearing mice an inhibition of PDE5 with sildenafil prolongs survival of the animals through the augmentation of antitumor immunity, indicating the immunomodulatory properties of this drug. Effects of sildenafil o...

Citations

... It was revealed that transcription factor STAT3 was promoted significantly, which might regulate the PD-L1 expression and M2 polarization. 32,35 For further verification, the expression of p-MerTK/ MerTK, p-p38/p38, and p-STAT3/STAT3 was detected after 15, 30, 60, 120, and 240 min of efferocytosis. With MerTK KD, we found that the phosphorylation of p38 (p-p38/p38) and STAT3 (p-STAT3/STAT3) was inhibited significantly (Figure 4c-e), as well as the attenuated expression of PD-L1 and Arg1 (Figure 4c,f,g). ...
... Enrichment of G-MDSCs further led to tumor progression, accompanied by a decrease in monocyte MDSC frequency. And it is worth noting that even after tumor resection, the MDSC cells in the peripheral blood of patients are still high, which may be related to tumor micrometastasis (53). Takeuchi et al. reported that the production of GM-CSF was significantly enhanced in various PDAC cell lines or PDAC tumor FIGURE 4 Mast cells are divided into tryptase/chymase-positive mast cells, MCCs, and MCTs according to their contents. ...
... 10 In our recent research, we deeply investigated this mouse strain and showed that B7-H1 deficiency in vivo modulates several immunological parameters, including the amount and composition of Gr1 + CD11b + myeloid population, the composition and activation state of the DC compartment, the frequency and status of natural killer (NK) and NKT cells, B cells, naïve/memory state of CD8 T cells, production of IL-2 and IL-10 cytokines, and increased PD-1 expression in the immune cells. 11 All these data underline the importance of B7-H1 as a decisive immune regulatory molecule. ...
... Taking into account the ubiquitous expression of PD-L1 receptor (PD-1) on non-myeloid specific immune cells (CD8, CD4 and Treg), our results indicate that immunotherapy with IFNα could lead to an undesirable side effect of general immunosuppression and consequently to increased tumor immune evasion or chronification of infection. Our data could also explain the insufficiency of IFNα therapy observed in several models, despite its promising in vitro and immunomonitoring results (41)(42)(43)(44). We propose that the combination of IFNα with checkpoint inhibitors like PD-L1 blocking antibody, could repress this immunosuppressive path and improve the efficiency of IFNα therapy by uncoiling the immune costimulatory potential of IFNα. ...
... Consistent with the MDSC data, Sildenafil had no effect on the frequency of control monocytes ( Figure 2D). This finding is consistent with our data in Appendix 1B and the literature, where Sildenafil had a lack of influence on the cytotoxicity of mononuclear cells (CD8 + , NKT, and NK cells) (61). Taken together, Sildenafil, at the concentration tested here, had no effect on the frequency of innate immune cells. . ...