Detection of intra-tumor self antigen recognition during melanoma tumor progression in mice using advanced multimode confocal/two photon microscope Journal Article
| Authors: | Schaer, D. A.; Li, Y.; Merghoub, T.; Rizzuto, G. A.; Shemesh, A.; Cohen, A. D.; Avogadri, F.; Toledo-Crow, R.; Houghton, A. N.; Wolchok, J. D. |
| Article 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. © 2011 Schaer et al. |
| Keywords: | controlled study; unclassified drug; nonhuman; cd8+ t lymphocyte; lymphocyte proliferation; animal cell; mouse; melanoma; animal experiment; animal model; tumor regression; tumor antigen; antigen; gamma interferon; antigen recognition; tumor cell; adoptive transfer; tumor growth; cytokine release; ex vivo study; cell interaction; cell motility; protein ot 1; protein pmel 1; self antigen; advanced multimode confocal microscope; microscope; two photon microscope |
| Journal Title: | PLoS ONE |
| Volume: | 6 |
| Issue: | 6 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2011-01-01 |
| Start Page: | e21214 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0021214 |
| PROVIDER: | scopus |
| PMCID: | PMC3120835 |
| PUBMED: | 21731676 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "Article No.: e21214" - "Source: Scopus" |
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