Unknown

Dataset Information

0

Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment.


ABSTRACT: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate during tumor formation, facilitate immune escape, and enable tumor progression. MDSCs are important contributors to the development of an immunosuppressive tumor microenvironment that blocks the action of cytotoxic antitumor T effector cells. Heterogeneity in these cells poses a significant barrier to studying the in vivo contributions of individual MDSC subtypes. Herein, we show that granulocyte-macrophage colony stimulating factor, a cytokine critical for the numeric and functional development of MDSC populations, promotes expansion of a monocyte-derived MDSC population characterized by expression of CD11b and the chemokine receptor CCR2. Using a toxin-mediated ablation strategy to target CCR2-expressing cells, we show that these monocytic MDSCs regulate entry of activated CD8 T cells into the tumor site, thereby limiting the efficacy of immunotherapy. Our results argue that therapeutic targeting of monocytic MDSCs would enhance outcomes in immunotherapy.

SUBMITTER: Lesokhin AM 

PROVIDER: S-EPMC3288305 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment.

Lesokhin Alexander M AM   Hohl Tobias M TM   Kitano Shigehisa S   Cortez Czrina C   Hirschhorn-Cymerman Daniel D   Avogadri Francesca F   Rizzuto Gabrielle A GA   Lazarus John J JJ   Pamer Eric G EG   Houghton Alan N AN   Merghoub Taha T   Wolchok Jedd D JD  

Cancer research 20111215 4


Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate during tumor formation, facilitate immune escape, and enable tumor progression. MDSCs are important contributors to the development of an immunosuppressive tumor microenvironment that blocks the action of cytotoxic antitumor T effector cells. Heterogeneity in these cells poses a significant barrier to studying the in vivo contributions of individual MDSC subtypes. Herein, we show that granulocyte-macr  ...[more]

Similar Datasets

| S-EPMC7051186 | biostudies-literature
| S-EPMC9053130 | biostudies-literature
| S-EPMC8039399 | biostudies-literature
| S-EPMC6721845 | biostudies-literature
| S-EPMC10017706 | biostudies-literature
| S-EPMC6272093 | biostudies-literature
| S-EPMC5544943 | biostudies-literature
| S-EPMC9293984 | biostudies-literature
| S-EPMC4735296 | biostudies-literature
| S-EPMC5783858 | biostudies-other