title: Detection of intra-tumor self antigen recognition during melanoma tumor progression in mice using advanced multimode confocal/two photon microscope.
abstract: Determining how tumor immunity is regulated requires understanding the extent to which the anti-tumor immune response "functions" in vivo without therapeutic intervention. To better understand this question, we developed advanced multimodal reflectance confocal/two photon fluorescence intra-vital imaging techniques to use in combination with traditional ex vivo analysis of tumor specific T cells. By transferring small numbers of melanoma-specific CD8+ T cells (Pmel-1), in an attempt to mimic physiologic conditions, we found that B16 tumor growth alone was sufficient to induce naive Pmel-1 T cell proliferation and acquisition of effector phenotype. Tumor -primed Pmel-1 T cells, are capable of killing target cells in the periphery and secrete IFNγ, but are unable to mediate tumor regression. Within the tumor, Pmel-1 T cells have highly confined mobility, displaying long term interactions with tumor cells. In contrast, adoptively transferred non tumor-specific OT-I T cells show neither confined mobility, nor long term interaction with B16 tumor cells, suggesting that intra-tumor recognition of cognate self antigen by Pmel-1 T cells occurs during tumor growth. Together, these data indicate that lack of anti-tumor efficacy is not solely due to ignorance of self antigen in the tumor microenvironment but rather to active immunosuppressive influences preventing a protective immune response.
authors: Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, United States of America.
authors: David A
authors: DA
authors: Schaer
authors: Yongbiao
authors: Y
authors: Li
authors: Taha
authors: T
authors: Merghoub
authors: Gabrielle A
authors: GA
authors: Rizzuto
authors: Amos
authors: A
authors: Shemesh
authors: Adam D
authors: AD
authors: Cohen
authors: Yanyun
authors: Y
authors: Li
authors: Francesca
authors: F
authors: Avogadri
authors: Ricardo
authors: R
authors: Toledo-Crow
authors: Alan N
authors: AN
authors: Houghton
authors: Jedd D
authors: JD
authors: Wolchok
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002450:Cell Communication; D049109:Cell Proliferation; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D000939:Epitopes