TY  - JOUR
A1  - Feigl, Frederik Fabian
A1  - Stahringer, Anika
A1  - Peindl, Matthias
A1  - Dandekar, Gudrun
A1  - Koehl, Ulrike
A1  - Fricke, Stephan
A1  - Schmiedel, Dominik
T1  - Efficient redirection of NK cells by genetic modification with chemokine receptors CCR4 and CCR2B
JF  - International Journal of Molecular Sciences
N2  - Natural killer (NK) cells are a subset of lymphocytes that offer great potential for cancer immunotherapy due to their natural anti-tumor activity and the possibility to safely transplant cells from healthy donors to patients in a clinical setting. However, the efficacy of cell-based immunotherapies using both T and NK cells is often limited by a poor infiltration of immune cells into solid tumors. Importantly, regulatory immune cell subsets are frequently recruited to tumor sites. In this study, we overexpressed two chemokine receptors, CCR4 and CCR2B, that are naturally found on T regulatory cells and tumor-resident monocytes, respectively, on NK cells. Using the NK cell line NK-92 as well as primary NK cells from peripheral blood, we show that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing the natural effector functions. This approach has the potential to enhance the therapeutic effect of immunotherapies in solid tumors by directing genetically engineered donor NK cells to tumor sites. As a future therapeutic option, the natural anti-tumor activity of NK cells at the tumor sites can be increased by co-expression of chemokine receptors with chimeric antigen receptors (CAR) or T cell receptors (TCR) on NK cells can be performed in the future.
KW  - chemokine receptor
KW  - migration
KW  - immune cell infiltration
KW  - trafficking
KW  - NK cells
KW  - immunotherapy
KW  - CCR2
KW  - CCR4
KW  - genetic engineering
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304049
SN  - 1422-0067
VL  - 24
IS  - 4
ER  - 
TY  - JOUR
A1  - Behr, Daniel S.
A1  - Peitsch, Wiebke K.
A1  - Hametner, Christian
A1  - Lasitschka, Felix
A1  - Houben, Roland
A1  - Schönhaar, Kathrin
A1  - Michel, Julia
A1  - Dollt, Claudia
A1  - Goebeler, Matthias
A1  - Marx, Alexander
A1  - Goerdt, Sergij
A1  - Schmieder, Astrid
T1  - Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas
JF  - International Journal of Clinical and Experimental Pathology
N2  - Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival.
KW  - CD8(+)
KW  - PD-L1
KW  - tertiary lymphoid structures
KW  - immune cell infiltration
KW  - polymavirus
KW  - survival
KW  - lymphocytes
KW  - responses
KW  - lung cancer
KW  - B-cells
KW  - breast cancer
KW  - antitumor immunity
KW  - T-antigens
KW  - Merkel cell carcinoma
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117720
SN  - 1936-2625
VL  - 7
IS  - 11
ER  -