The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights
from the Saturday programs (Nov. 11, 2017) of the 32nd Annual Meeting in National Harbor, Md. (Scroll to the bottom of this blog post to view the Glossary).
Dendritic cell acquisition of MHC I controls CD8+ T cell priming
Brandon MacNabb, BS (University of Chicago) presented data
supporting the concept of MHC I antigen presentation by Batf3-lineage DCs as a
critical component of CD8+-mediated anti-tumor response. Researchers initially
generated H2-KbAB (MHC I+) and Kb-/-(MHC I-) C1498.SIY acute myeloid leukemia
cell lines and subsequently engrafted C57BL/6 mice to determine the
contribution of tumor cell MHC I presentation in CD8+ T cell priming. Initial
assessment revealed reduced tumor growth in C1498.SIY KbAB mice compared to
C1498.SIY Kb-/- mice. CD8+ T cell proliferation was also increased in KbAB mice
compared to Kb-/- mice (p < 0.05). The observed C1498.SIY KbAB-dependent CD8+
proliferation was abolished in Batf3-/- C57BL/6 mice (p < 0.01). IFN-ϒ
secretion was also decreased in Batf3-/- KbAB mice, suggesting that Batf3
initiates CD8+ priming. Transfer of autologous T cells from KbAB tumor-bearing mice
offered complete protection from tumor growth in tumor-free mice. Conversely, autologous
T cells from Kb-/- mice offered no such protection. Interestingly, DCs isolated
from the TME and the tumor-draining lymph node in tumor-positive mice had
increased KbAB MHC I expression (p < 0.001), suggesting DC acquisition of
tumor-derived MHC I. Ex vivo experiments confirmed that migratory KbAB DCs are
capable of CD8+ priming. These data reveal the importance of Batf3-lineage DCs
and tumor-derived MHC I presentation in CD8+ T cell activation of anti-tumor
response, providing insight into potential development of DC-oriented
therapies.
