Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment

• DOI: 10.1073/pnas.0911378107
• Publication Date: 2010-04-20T03:40:15Z
• Authors: G-One Ahn; Diane Tseng; Cho-Hwa Liao; Mary Jo Dorie; Agnieszka Czechowicz; J. Martin Brown
• Keywords: 0301 basic medicine; BONE-MARROW; LEUKOCYTE ADHESION; Macrophage-1 Antigen; Mice, Nude; MOUSE; ANGIOGENESIS; Antibodies; ADHESION MOLECULES; vasculogenesis; Cell Line; Mice; 03 medical and health sciences; Cell Movement; Recurrence; Animals; Humans; Myeloid Cells; MACROPHAGES; S100A8; Mice, Knockout; CD11b Antigen; Xenograft Model Antitumor Assays; 3. Good health; Disease Models, Animal; MONOCYTES; radiosensitivity; CARCINOMAS; CD18 Antigens; METASTASIS; Carcinoma, Squamous Cell; RADIOTHERAPY

Despite recent advances in radiotherapy, loco-regional failures are still the leading cause of death many cancer patients. We have previously reported that bone marrow-derived CD11b + myeloid cells recruited to tumors grown irradiated tissues, thereby restoring vasculature and tumor growth. In this study, we examined whether neutralizing monoclonal antibodies could inhibit recruitment into their regrowth. observed a significant enhancement antitumor response radiation squamous cell carcinoma xenografts mice when administered systemically. Histological examination revealed reduced infiltration expressing S100A8 matrix metalloproteinase-9. further inhibited adhesion transmigration C166 endothelial monolayers chemotactic stimuli, respectively, levels comparable those from knockout or CD18 hypomorphic mice. Given clinical availability humanized antibodies, tested two murine models found were more sensitive irradiation but not When hypomorphism was partially rescued by reconstitution with wild-type marrow, resistance restored. Our study thus supports rationale using clinically available Mac-1 (CD11b/CD18) as an adjuvant therapy radiotherapy.