What question did this study set out to answer?

To determine whether targeting CXCR2-driven trafficking of myeloid-derived suppressor cells overcomes resistance to anti-PD1 immune checkpoint blockade in rhabdomyosarcoma.

May 21, 2014Science Translational MedicineOpen Access

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy

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To determine whether targeting CXCR2-driven trafficking of myeloid-derived suppressor cells overcomes resistance to anti-PD1 immune checkpoint blockade in rhabdomyosarcoma.
Assessed PD-L1 expression, MDSC infiltration, and the timing of anti-PD1 efficacy in murine rhabdomyosarcoma models.
Evaluated the impact of genetic CXCR2 knockout and anti-CXCR2 monoclonal antibody therapy on MDSC tumor trafficking and delayed anti-PD1 treatment efficacy.
Quantified serum CXCR2 ligands (including CXCL8) in pediatric sarcoma patients and analyzed their correlation with patient survival.
Early anti-PD1 therapy prevented tumor growth, but delayed therapy failed due to local accumulation of immunosuppressive CXCR2(+)CD11b(+)Ly6G(hi) MDSCs.
Genetic CXCR2 deficiency or pharmacological blockade with anti-CXCR2 antibodies stopped MDSC trafficking to the tumor bed and restored the antitumor efficacy of delayed anti-PD1 therapy.
Patients with metastatic pediatric sarcomas exhibited elevated circulating CXCR2 ligands, and elevated CXCL8 was significantly associated with reduced overall survival.

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Implication

Preclinical study shows that blocking CXCR2-mediated MDSC trafficking restores anti-PD1 efficacy in rhabdomyosarcoma, highlighting a strategy to overcome immunotherapy resistance.

Cite This Study

Highfill et al. (2014) studied this question.

synapsesocial.com/papers/69d78d556cc86f5f11b8a47d https://doi.org/10.1126/scitranslmed.3007974

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Implication

Preclinical study shows that blocking CXCR2-mediated MDSC trafficking restores anti-PD1 efficacy in rhabdomyosarcoma, highlighting a strategy to overcome immunotherapy resistance.

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy

Key Points

Discussion

Implication

Cite This Study

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy

Key Points

Discussion

Implication

Cite This Study

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