title: Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells.
abstract: Recruitment of effector T cells to inflamed peripheral tissues is regulated by chemokines and their receptors, but the factors regulating recruitment to tumors remain largely undefined. Ionizing radiation (IR) therapy is a common treatment modality for breast and other cancers. Used as a cytocidal agent for proliferating cancer cells, IR in combination with immunotherapy has been shown to promote immune-mediated tumor destruction in preclinical studies. In this study we demonstrate that IR markedly enhanced the secretion by mouse and human breast cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells, and plays an important role in their recruitment to sites of inflammation. Using a poorly immunogenic mouse model of breast cancer, we found that irradiation increased the migration of CD8(+)CXCR6(+) activated T cells to tumors in vitro and in vivo. CXCR6-deficient mice showed reduced infiltration of tumors by activated CD8 T cells and impaired tumor regression following treatment with local IR to the tumor and Abs blocking the negative regulator of T cell activation, CTLA-4. These results provide the first evidence that IR can induce the secretion by cancer cells of proinflammatory chemotactic factors that recruit antitumor effector T cells. The ability of IR to convert tumors into "inflamed" peripheral tissues could be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy.
authors: Department of Pathology, New York University School of Medicine, New York, USA.
authors: Satoko
authors: S
authors: Matsumura
authors: Baomei
authors: B
authors: Wang
authors: Noriko
authors: N
authors: Kawashima
authors: Steve
authors: S
authors: Braunstein
authors: Michelle
authors: M
authors: Badura
authors: Thomas O
authors: TO
authors: Cameron
authors: James S
authors: JS
authors: Babb
authors: Robert J
authors: RJ
authors: Schneider
authors: Silvia C
authors: SC
authors: Formenti
authors: Michael L
authors: ML
authors: Dustin
authors: Sandra
authors: S
authors: Demaria
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology / Q000528:radiation effects*; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism / Q000528:radiation effects*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011839:Radiation, Ionizing; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D051116:Receptors, Scavenger / Q000235:genetics / Q000528:radiation effects*; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D051116:Receptors, Scavenger