Unknown

Dataset Information

0

Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors.


ABSTRACT: Type 2 DCs (DC2s) comprise the majority of conventional DCs within most tumors; however, little is known about their ability to initiate and sustain antitumor immunity, as most studies have focused on antigen cross-presenting DC1s. Here, we report that DC2 infiltration identified by analysis of multiple human cancer data sets showed a significant correlation with survival across multiple human cancers, with the benefit being seen in tumors resistant to cytotoxic T cell control. Characterization of DC subtype infiltration into an immunotherapy-resistant model of breast cancer revealed that impairment of DC1s through 2 unique models resulted in enhanced DC2 functionality and improved tumor control. BATF3 deficiency depleted intratumoral DC1s, which led to increased DC2 lymph node migration and CD4+ T cell activation. Enhancing DC2 stimulatory potential by genetic deletion of Hsp90b1 (encoding molecular chaperon GP96) led to a similar enhancement of T cell immunity and improved survival in a spontaneous breast cancer model. These data highlight the therapeutic and prognostic potential of DC2s within checkpoint blockade-resistant tumors.

SUBMITTER: Iwanowycz S 

PROVIDER: S-EPMC8492342 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7228660 | biostudies-literature
| S-EPMC3817614 | biostudies-literature
| S-EPMC3009819 | biostudies-other
| S-EPMC8094935 | biostudies-literature
| S-EPMC7269842 | biostudies-literature
| S-EPMC4101877 | biostudies-literature
| S-EPMC3897521 | biostudies-literature
| S-EPMC2892234 | biostudies-literature
| S-EPMC3545652 | biostudies-literature
| S-EPMC3159799 | biostudies-literature