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Abstracts (complete list) - Wissenschaft Online

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Fanny Edele, Cindy Reinhold, Stefan F. Martin<br />

Efficiency of T cell defence against melanoma depends on the<br />

DC immunization route<br />

We have recently shown that different routes of DC immunization induce effector/<br />

memory CD8+ T cells expressing different arrays of tissue-specific homing receptors.<br />

This polarization is driven in vivo by tissue-specific DC. In our current study, we<br />

investigate the role of homing receptor polarization by DC vaccination for the efficiency<br />

of anti-tumor immunity in the mouse model of B16.F10 melanoma. We use the parental<br />

tumor as well as B16.F10GP33 that expresses a T cell epitope from the glycoprotein of<br />

lymphocytic choriomeningitis virus (LCMV).<br />

We examined the role of different DC immunization routes for the homing of T cell<br />

receptor transgenic P14 effector/memory T cells and wild type T cells that recognize<br />

GP33 and its correlation with the ability to control tumor growth.<br />

We adoptively transferred naive P14 T cells and activated them in vivo with GP33pulsed<br />

DC via the intracutaneous (i.c.), i.v. or i.p. route. After subcutaneous inoculation<br />

of B16.F10 or B16.F10GP33 melanoma cells into the left and right flanks of C57BL/6<br />

mice, respectively, tumor size was measured every 2 days. DC-GP33 prevented the<br />

growth of B16.F10GP33 tumor in all groups independent of the immunization route.<br />

Thus, induction of skin-specific homing receptors upon i.c. DC injection or the lack of a<br />

tissue-specific polarization or flexible reprogramming when DC are injected i.v. or i.p.,<br />

respectively, allow efficient tumor defence in this setting. However, a different outcome<br />

was observed in recipient mice when no P14 T cells were transferred. In this case, longterm<br />

protective immunity against B16.F10GP33 melanoma required the induction of<br />

skin-specific CD8+ T cells by immunization with DC-GP33 via the i.c. route. Thus, tissuetargeting<br />

of tumor antigen-specific effector T cells by the appropriate DC vaccination<br />

route determines the efficiency of the anti-tumor immune response.<br />

Our findings are relevant for the biological therapy of human cancers.

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