detection of intra-tumor self antigen recognition during melanoma tumor progression in mice using advanced multimode confocaltwo photon microscope检测intra-tumor自我抗原识别在小鼠黑色素瘤肿瘤恶化期间使用先进的多模confocaltwo光子显微镜.pdfVIP

Detection of Intra-Tumor Self Antigen Recognition during Melanoma Tumor Progression in Mice Using Advanced Multimode Confocal/Two Photon Microscope David A. Schaer1., Yongbiao Li3., Taha Merghoub 1,2, Gabrielle A. Rizzuto 1,4, Amos Shemesh 1, Adam D. Cohen2¤, Yanyun Li 1, Francesca Avogadri 1, Ricardo Toledo-Crow3, Alan N. Houghton 1,2,4, Jedd D. Wolchok1,2,4* 1 Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, United States of America, 2 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 3 Research Engineering Lab, Sloan-Kettering Institute for Cancer Research, New York, New York, United States of America, 4 Weill Medical College of Cornell University, New York, New York, United States of America 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 IFNc, 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,