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Myeloid-derived suppressor cell (MDSC) is a heterogeneous myeloid cell population that can broadly be characterised as CD11b+Gr-1+ cells in mice. MDSC can be further classified into two main cell subsets, granulocytic MDSC (G-MDSC, CD11b+Ly6ClowLy6G+) and monocytic MDSC (M-MDSC, CD11b+Ly6ChighLy6G−).1 To address the role of MDSC in disease settings (eg, cancer and autoimmune disorders) and to evaluate the potential therapeutic benefits of targeting MDSC in preclinical models, different strategies, including anti-Gr-1 antibodies2–5 and pharmacological inhibitors (eg, gemcitabine and 5-fluorouracil),6 ,7 have been widely used to selectively remove mouse MDSC. The use of these reagents in combination with appropriate experimental systems has advanced significantly our current understanding of these myeloid cells in multiple physiological and pathological processes. Xing et al8 raised an issue with the use of anti-Gr-1 (RB6-8C5) for depletion of MDSC, which indeed has long been recognised by the research community. Anti-Gr-1 antibodies can bind to two Ly6 superfamily molecules, Ly6G and Ly6C, which are preferentially expressed on the granulocytes and monocytes, respectively. The differential expression levels of Gr-1 on G-MDSC and M-MDSC may result in different sensitivities to cross-linking of or depletion …