Journal Article

DKFZ-2021-00366

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression.

Groth, C. (First author)DKFZ* ; Arpinati, L. ; Shaul, M. E. ; Winkler, N.DKFZ* ; Diester, K. G.DKFZ* ; Gengenbacher, N.DKFZ* ; Weber, R.DKFZ* ; Arkhypov, I.DKFZ* ; Lasser, S.DKFZ* ; Petrova, V.DKFZ* ; Augustin, H. G.DKFZ* ; Altevogt, P.DKFZ* ; Utikal, J.DKFZ* ; Fridlender, Z. G. ; Umansky, V. (Last author)DKFZ*

2021
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/cancers13040726

Abstract: 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.

Keyword(s): CXCL1 ; CXCR2 ; PMN-MDSC ; genetically engineered mouse model ; immunosuppression ; immunotherapy ; melanoma ; metastasis

Note: #EA:A370#LA:A370#

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Contributing Institute(s):

1. KKE Dermatoonkologie (A370)
2. A190 Vaskuläre Onkologie und Metastatistierung (A190)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2021

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Database coverage:
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