Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice.
Recent studies show that the liver is a preferred organ for the accumulation of MDSC. In this study, we examined the effect of systemic RB6-8C5 treatment on hepatic MDSC in tumor-bearing mice. EL4 tumor-bearing mice were injected i.p. with RB6-8C5, and hepatic, splenic, and blood MDSCs were analyzed by flow cytometry. Unexpectedly, hepatic MDSC remained in the liver, although RB6-8C5 completely eliminated them from the spleen and peripheral blood 24 h after treatment. Secondary antibody staining confirmed the presence of RB6-8C5-bound MDSC in the liver of mice with s.c. tumors. Similar observations were made in two other (colon and melanoma) tumor models. Whereas RB6-8C5 injection induced cell death of hepatic MDSC, as shown by Annexin V/7-AAD staining, these cells were replaced immediately, leading to a constant, increased frequency of hepatic MDSC. Adoptively transferred MDSC migrated preferentially to the liver after RB6-8C5 treatment, suggesting that hepatic MDSCs are reconstituted rapidly after depletion. Finally, hepatic MDSC remained immunosuppressive despite RB6-8C5 injection. Our study demonstrates that RB6-8C5 is not suitable for depletion of hepatic MDSCs and analysis of their function.
Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Chi
C
Ma
Tamar
T
Kapanadze
Jaba
J
Gamrekelashvili
Michael P
MP
Manns
Firouzeh
F
Korangy
Tim F
TF
Greten
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D047589:Leukocyte Reduction Procedures; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine