TY  - JOUR
AU  - Groth, Christopher
AU  - Arpinati, Ludovica
AU  - Shaul, Merav E
AU  - Winkler, Nina
AU  - Diester, Klara Gabriele
AU  - Gengenbacher, Nicolas
AU  - Weber, Rebekka
AU  - Arkhypov, Ihor
AU  - Lasser, Samantha
AU  - Petrova, Vera
AU  - Augustin, Hellmut G
AU  - Altevogt, Peter
AU  - Utikal, Jochen
AU  - Fridlender, Zvi G
AU  - Umansky, Viktor
TI  - Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression.
JO  - Cancers
VL  - 13
IS  - 4
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2021-00366
SP  - 726
PY  - 2021
N1  - #EA:A370#LA:A370#
AB  - Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression.Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas.Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells.We provide evidence for the tumor-promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.
KW  - CXCL1 (Other)
KW  - CXCR2 (Other)
KW  - PMN-MDSC (Other)
KW  - genetically engineered mouse model (Other)
KW  - immunosuppression (Other)
KW  - immunotherapy (Other)
KW  - melanoma (Other)
KW  - metastasis (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33578808
DO  - DOI:10.3390/cancers13040726
UR  - https://inrepo02.dkfz.de/record/167462
ER  -