Innate immune recognition of breast tumor cells mediates CCL22 secretion favoring Treg recruitment within tumor environment

Abstract

Regulatory T cells (Treg) have been reported of poor prognosis for overall survival in primary breast tumors (BT). As CCL22 plays a major role in Treg recruitment within primary BT we deciphered the mechanisms involved in the CCL22 production by breast epithelial tumor cells and propose herein the major role of their innate immune recognition in this production.

Figure 1. Scheme recapitulating the sequence of events leading to the strong non polarized CCL22 production by tumor cells. Healthy epithelial cells secrete low levels of CCL22 in a polarized manner within the luminal acini, their transformation favor their recognition by infiltrating NK cells leading to IFNγ secretion. IFNγ promoted macrophage activation that will produce TNFα and IL-1β after interaction with breast epithelial tumor cells. Combined action of IFNγ, IL-1β and TNFα will induce non polarized strong CCL22 secretion by tumor cells that will induce the recruitment of CCR4⁺ Treg from periphery, leading to CCR4 internalization.