CD8α+ DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumor
McDonnell, A.M., Prosser, A.C., van Bruggen, I., Robinson, B.W.S. and Currie, A.J. (2010) CD8α+ DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumor. European Journal of Immunology, 40 (6). pp. 1617-1627.
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One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8+ T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-presenting DC using a solid tumor model expressing a membrane bound neo-antigen (hemagglutinin, HA). Tumor antigen was constitutively cross-presented in the tumor-draining LN throughout tumor progression by CD11c+ DC. Further analysis revealed that both CD8α+ and CD8α− DC subsets, but not plasmacytoid DC, were effective at cross-presenting HA tumor antigen. The proportions of DC subsets in the tumor-draining LN were equivalent to those seen in the LN of naïve mice; however, a significant increase in the expression of the potential inhibitory B7 molecule, B7-DC, was noted and appeared to be restricted to the CD8α– DC subset. Therefore LN resident CD8α+ DC are not the sole DC subset capable of cross-presenting cell-associated tumor antigens. Migratory tumor DC subsets with altered co-stimulatory receptor expression may contribute to induction and regulation of tumor-specific responses.
|Publication Type:||Journal Article|
|Publisher:||John Wiley & Sons Ltd.|
|Copyright:||© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim|
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