Tumour-infiltrating CD11b+ myelomonocytes and response to fractionated irradiation of human squamous cell carcinoma (hSCC) xenografts

Abstract Purpose Bone marrow derived CD11b+ myelomonocytes have been shown to be recruited by the tumour and to promote tumour regrowth after irradiation. Here we investigated in a panel of well characterised hSCC tumour models the number of tumour-infiltrating CD11b+ cells and the association with response to clinically relevant fractionated irradiation. Methods Six hSCC tumour models (UT-SCC-5, -14, -15, XF354, FaDu, SAS) xenografted in nude mice were excised after injection of pimonidazole hypoxia marker before irradiation and after 5 and 10 fractions. In parallel, TCD 50 (dose to cure 50% of the tumours) assays were performed to determine the response to 30 fractions within 6 weeks. The TCD 50 values have been previously published [1] . Double staining of CD11b and pimonidazole was performed using immunofluorescence. CD11b+ cells were counted in viable pimonidazole-negative areas (non-hypoxic) and pimonidazole-positive areas (hypoxic) of whole tumour cross-sections. Results The median number of tumour-infiltrating CD11b+ cells either decreased or remained unchanged after 5 and 10 fractions in most of the tumour models. The density of CD11b+ cells in hypoxic areas was similar or lower than in non-hypoxic regions independently on treatment in majority of the tumour models. After 10 fractions the median CD11b+ cell density was significantly associated with the TCD 50 values after 30 fractions. Conclusion The data from our exploratory study suggest that tumour-infiltrating CD11b+ cells may contribute to local tumour control after fractionated irradiation, which supports to further study their prognostic value and to evaluate specific myelomonocyte targeting strategies to overcome radiation resistance.