Table 2

Non-canonical programmed cell death 1 (PD-1) signaling in stromal cells

Cell typeCancer typeBiology effectPotential implication in clinicRef
TregsHuman gastric cancer, mouse implanted tumor model (B16F0)Promoting Tregs proliferation and immunosuppressive activityContribution of PD-1+ Tregs to HPD during PD-1 blockade therapy23
Mouse implanted tumor model (B16F10)PD-1 signaling maintain the expression of FOXP3 through proteolytic pathwayNA45
B cellsHuman hepatoma, mouse orthotopic hepatoma (Hepa1-6)Promoting tumor growth via secretion of IL-10Contribution of B cells to efficacy of PD-1 blockade therapy.25
NKsMouse implanted tumor model (RMA-S, CT26, 4T1)Suppressing NKs mediated tumor controlContribution of NK cells to efficacy of PD-1 blockade therapy.27
Human head and neck cancerInhibiting activation and cytotoxicity of NKsContribution of NK cells to efficacy of PD-1 blockade therapy.144
TAMsHuman colorectal cancer and mouse implanted tumor model (CT26)Inhibiting phagocytic capacity against tumor cellsContribution of TAMs to efficacy of PD-1 blockade therapy.26
Human gastric cancerInhibiting phagocytic capacity against tumor cellsPD-1+ TAMs infiltration correlate with unfavorable prognosis in gastric cancer118
Myeloid cellsMouse implanted tumor model (B16F10, MC38)Inhibiting differentiation of myeloid cells by restraining cholesterol.Contribution of myeloid cells to efficacy of PD-1 blockade therapy.119
DCsHuman ovarian cancer (tumor tissue and ascites), mouse implanted tumor model (ID8, intraperitoneally)Inhibiting NF-kB-mediated antigen presentation in a SHP-2-independent mannerContribution of NKs to efficacy of PD-1 blockade therapy.28
Human ovarian cancerPromoting IL-10 productionCombined PD-1 blockade with IL-10 neutralization shows synergistic effect.29
Mouse implanted tumor model (ID8, intraperitoneally)Promoting polarization toward an immunosuppressive and immature state by inhibiting NF-kB.NA124
  • DCs, dendritic cells; HPD, hyperprogressive disease; IL, interleukin; NA, not available; NKs, natural killer cells; TAMs, tumor-associated macrophage; Treg, regulatory T cells.