Table 2.
Non-canonical programmed cell death 1 (PD-1) signaling in stromal cells
| Cell type | Cancer type | Biology effect | Potential implication in clinic | Ref |
| Tregs | Human gastric cancer, mouse implanted tumor model (B16F0) | Promoting Tregs proliferation and immunosuppressive activity | Contribution of PD-1+ Tregs to HPD during PD-1 blockade therapy | 23 |
| Mouse implanted tumor model (B16F10) | PD-1 signaling maintain the expression of FOXP3 through proteolytic pathway | NA | 45 | |
| B cells | Human hepatoma, mouse orthotopic hepatoma (Hepa1-6) | Promoting tumor growth via secretion of IL-10 | Contribution of B cells to efficacy of PD-1 blockade therapy. | 25 |
| NKs | Mouse implanted tumor model (RMA-S, CT26, 4T1) | Suppressing NKs mediated tumor control | Contribution of NK cells to efficacy of PD-1 blockade therapy. | 27 |
| Human head and neck cancer | Inhibiting activation and cytotoxicity of NKs | Contribution of NK cells to efficacy of PD-1 blockade therapy. | 144 | |
| TAMs | Human colorectal cancer and mouse implanted tumor model (CT26) | Inhibiting phagocytic capacity against tumor cells | Contribution of TAMs to efficacy of PD-1 blockade therapy. | 26 |
| Human gastric cancer | Inhibiting phagocytic capacity against tumor cells | PD-1+ TAMs infiltration correlate with unfavorable prognosis in gastric cancer | 118 | |
| Myeloid cells | Mouse 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 |
| DCs | Human ovarian cancer (tumor tissue and ascites), mouse implanted tumor model (ID8, intraperitoneally) | Inhibiting NF-kB-mediated antigen presentation in a SHP-2-independent manner | Contribution of NKs to efficacy of PD-1 blockade therapy. | 28 |
| Human ovarian cancer | Promoting IL-10 production | Combined 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. | NA | 124 |
DCs, dendritic cells; HPD, hyperprogressive disease; IL, interleukin; NA, not available; NKs, natural killer cells; TAMs, tumor-associated macrophage; Treg, regulatory T cells.