Play all audios:
Access through your institution Buy or subscribe The authors analysed the different tumour-infiltrating antigen presenting cells (APCs) in a modified spontaneous breast tumour model —
polyoma middle T antigen, engineered to express mCherry and ovalbumin (PyMTChOVA). Tumoural dendritic cells (DCs) were distinguished from macrophages based on CD24hi and F4/80lo expression.
Two populations of DCs, namely CD11b+ and CD103+ DCs (previously described in healthy tissues) were identified within breast tumours, and were also found to exist in two mouse models of
melanoma as well as multiple additional mouse tumours. Similarly, two populations of tumour-associated macrophages (TAMs) were also identified: CD11clo CD11bhi TAMs and CD11chi CD11blo TAMs,
which were also present in all tumour models analysed. These TAM and DC populations were also found in human metastatic melanoma biopsies. Consistent across all mouse and human samples was
the rarity of the CD11b+ and CD103+ DC populations, with CD103+ DCs being particularly sparse. To further characterize these APCs, the authors analysed their gene expression profiles. The
four populations could be clearly segregated, with the TAMs and CD11b+ DCs sharing most of the macrophage-specific makers, and CD103+ DCs showing the most distinct transcriptional profile.
Among the genes most distinctly expressed were DC-defining transcription factors, such as interferon regulatory factor 8 (_IRF8_; specific for CD103+ DC alone), zinc finger and BTB
domain-containing protein 46 (_ZBTB46_; specific for both sets of DCs), and _IRF4_ (enriched in CD11b+ DCs). Knocking down the expression of these genes showed that the different tumoural
APC populations rely on these transcription factors to different extents. In a PyMT ectopic breast tumour model, loss of _Irf8_ specifically ablated CD103+ DCs but did not affect TAMs. In
the B78ChOVA model, deletion of _Irf4_ resulted in the specific reduction of CD11b+ DCs with little change in the other cell populations. Deletion of _Batf3_ resulted in ablation of the
CD103+ DC population, with no effect on the numbers of CD11b+ DCs or TAMs, showing that CD103+ DCs represent a distinct lineage of APC in the tumour. This is a preview of subscription
content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue
Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL
ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Broz, M. L. et al. Dissecting the tumor myeloid compartment reveals
rare activating antigen-presenting cells critical for T cell immunity. _Cancer Cell_ http://dx.doi.org/10.1016/j.ccell.2014.09.007 (2014) Download references Authors * M. Teresa Villanueva
View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Villanueva, M. The
new midfielders in the tumour microenvironment. _Nat Rev Cancer_ 14, 765 (2014). https://doi.org/10.1038/nrc3861 Download citation * Published: 30 October 2014 * Issue Date: December 2014 *
DOI: https://doi.org/10.1038/nrc3861 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not
currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative