title: Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
abstract: FoxP3(+) T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3(+) regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3(+) T cells. We found that only memory, but not naïve, FoxP3(+) T cells are highly enriched in tumors. Almost all of the tumor-infiltrating FoxP3(+) T cells express Helios, an antigen associated either with thymus-generated FoxP3(+) T cells or activated T cells in the periphery. The tumor-infiltrating FoxP3(+) T cells largely lack CD62L and CCR7, two trafficking receptors required for T cell migration into secondary lymphoid tissues. Instead, the tumor infiltrating FoxP3(+) T cells highly express memory/tumor-associated CCR8 and CXCR4. Antigen priming is required for induction of this trafficking receptor phenotype in FoxP3(+) T cells and only antigen primed, but not antigen-inexperienced naive, FoxP3(+) T cells can efficiently migrate into tumors. While the migration of FoxP3(+) T cells into tumors was a readily detectable event, generation of induced FoxP3(+) T cells within tumors was unexpectedly inefficient. Genetic marking of current and ex-FoxP3(+) T cells revealed that tumor-infiltrating FoxP3(+) T cells are highly stable and do not readily convert back to FoxP3(-) T cells. Taken together, our results indicate that population of tumors with thymus-generated FoxP3(+) T cells requires an antigen priming-dependent trafficking receptor switch in lymphoid tissues.
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue Cancer Center, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Wang
authors.forename: Jee H
authors.initials: JH
authors.lastname: Lee
authors.forename: Chang H
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D055261:Immunogenetic Phenomena / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019707:Receptors, Chemokine; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse