Dendritic cells (DC) are pivotal antigen-presenting cells within the tumor immune microenvironment (TIME) and play a critical role in cancer immunity. To uncover their clinical relevance, plasmacytoid DC (pDC) and conventional DC (cDC) infiltration were thoroughly studied in extensive patient cohorts using advanced transcriptomic analyses.
The groundbreaking findings showed that high levels of pDC were significantly associated with improved survival in triple negative breast cancer (TNBC), whereas cDC did not show the same correlation. Remarkably, high pDC presence in TNBC patients was linked to a higher fraction of anti-cancer immune cells and elevated expression of various immune checkpoint molecules.
These discoveries represent a milestone, as it is the first time that pDC’s crucial role in influencing the immune response and patient survival has been unveiled, surpassing the impact of cDC. Understanding the power of these specialized cells could pave the way for more targeted and effective treatments in the fight against TNBC.
Dendritic cells (DC) represent a major antigen-presenting cell in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Clinical relevance of plasmacytoid DC (pDC) and
conventional DC (cDC) infiltration were studied in large patient cohorts using transcriptomic analyses. We found that high pDC was significantly associated with better survival in triple negative breast cancer (TNBC), but not cDC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune checkpoint molecules examined. For the first time, we found that pDC are correlated with immune response and survival in TNBC patients more strongly than cDC.
Using the TCGA and METABRIC cohorts of breast cancer patients, we found that transcriptionally defined levels of cDC and pDC infiltration were elevated in TNBC compared to other subtypes of breast cancer. In contrast to high cDC infiltration, high pDC TNBC was significantly associated with favorable DSS and DFS. High cDC TNBC enriched not only immune and inflammation-related gene sets, but also metastasis-related gene sets, whereas high pDC TNBC had enriched immune and inflammation-related gene sets including IFN-γ more strongly than cDC. Both high cDC TNBC and high pDC TNBC were associated with anticancer immune cells, however, it was more consistent and robust with high pDC TNBC. We further found that pDC in TNBC was strongly positively correlated with the fraction of CD8+ T cells and CD4+ memory T
cells, and the level of IFN-γ score as well as cytolytic activity score, which suggests an overall anti-cancer immune microenvironment and immune activity. Interestingly, high pDC TNBC was significantly associated with the high expression of all the immune checkpoint molecules examined, the number of which is much larger than high cDC TNBC.
In conclusion, transcriptionally defined high cDC or pDC TNBC were associated with a favorable immune microenvironment. High pDC TNBC was strongly correlated with high immune function compared to cDCs. This is the first study suggesting that the pDC level may be more clinically relevant than cDCs in TNBC patients. pDC level may serve as a useful tool for identifying patients with better prognosis.
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