Senescence-associated secretory phenotype (SASP)-mediated immune cell
recruitment that favors tumor progression. The SASP has been described in
various contexts to create an immunosuppressive environment that drives tumor
progression. (A) In the liver, the SASP factor CCL2 acts to recruit immature
myeloid cells. However, combined with tumor-secreted factors, CCL2 drives
myeloid cells to block the maturation of macrophages and inhibit natural killer
(NK) cell activity, resulting in uninhibited tumor growth. (B) In skin, the SASP
factor IL-6 recruits Gr-1+ myeloid cells, regulatory T cells, and granulocytic
and monocytic myeloid-derived suppressor cells (MDSCs), which reduce CD8+ T cell
responsiveness. This immunosuppressive environment allows tumor cell
proliferation. (C) In the prostate, the SASP recruits Gr-1+ myeloid cells, which
secrete IL-1 receptor antagonist (IL-1RA). IL-1RA binds IL-1R, blocking
IL-1-mediated SASP production necessary for the induction of paracrine
senescence, thus allowing tumor growth.