Tumor microenvironment converts plasmacytoid dendritic cells into immunosuppressive/tolerogenic cells: insight into the molecular mechanisms

Human pDCs represent a rare population of circulating
cells characterized by a rapid and massive TLR-dependent
secretion of type I IFN in response to pathogenic
agents or danger signals. Through their capacity to bring
together innate and adaptive immunity and to secrete
soluble factors controlling cancer development, these
cells could represent important actors in antitumor immunity.
However, accumulating evidence suggests that
pDCs recruited to the tumor microenvironment often display
a nonactivated state and are associated with the development
and maintenance of immunosuppression.
Here, we present an overview of neoplastic lesions associated
with an infiltration of immunosuppressive/
tolerogenic pDC. Moreover, as the proper response of
pDC against cancer depends on a critical balance between
immune-activating and immune-suppressing
mechanisms, we summarize current knowledge about
the molecular pathways developed by tumors to prevent
antitumoral pDC immune responses. A better understanding
of the mechanisms regulating pDC function
in tumors could aid in the development of new therapies.
Indeed, effective cancer vaccines or therapies
could combine immunoactivating strategies (i.e., TLR
agonists) with elimination of immune-suppressing
mechanisms, leading to pDC reprogramming and thus,
allowing tumor rejection in a clinical setting.