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- Title
Detection of Intra-Tumor Self Antigen Recognition during Melanoma Tumor Progression in Mice Using Advanced Multimode Confocal/Two Photon Microscope.
- Authors
Schaer, David A.; Li, Yongbiao; Merghoub, Taha; Rizzuto, Gabrielle A.; Shemesh, Amos; Cohen, Adam D.; Li, Yanyun; Avogadri, Francesca; Toledo-Crow, Ricardo; Houghton, Alan N.; Wolchok, Jedd D.
- 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, adoptively transferred non tumorspecific OT-I T cells show neither confined mobility, nor long term interaction with B16 tumor cells, suggesting that intratumor 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.
- Subjects
CONFOCAL microscopy; MELANOMA; CANCER invasiveness; LABORATORY mice; TUMOR antigens; IMMUNE response; FLUORESCENCE microscopy; GLYCOPROTEINS
- Publication
PLoS ONE, 2011, Vol 6, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0021214