Table 1.
Effects of complement on the immune tumor microenvironment of different murine cancer models1.
| Tumor type2 | Cervical cancer (TC-1) |
Lung cancer (3LL) |
Ovarian cancer (transgenic Tg+) |
Ovarian cancer (SKOV-3) |
Lymphoma (RMA) |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Experimental model | C3 KO3 |
C5aR KO |
C5aR AP |
C5aR AP |
C5aR AA |
C3 KO |
C3 Het. |
C5aR KO |
C5atransfection (low expression) |
C5a transfection (low expression) |
C5a transfection (high expression) |
||
| Tumor growth | ↓ | ↓ | ↓ | ↓ | ↓ (n.s.) | ↓ | ↓ | ↓ | ↓ | ↓ | ↑ | ||
| Tumor | Immune cell populations | Total MDSCs | ↑ (n.s.) | = | = | ↑ (n.s.) | = | = | |||||
| MO-MDSC | = | ||||||||||||
| PMN-MDSCs | ↓ | ||||||||||||
| B cells | = | = | |||||||||||
| Macrophages | = | = | t | = | |||||||||
| CD8+ T cells | ↑ (n.s.) | ↑ (n.a.) | ↓ | = | = | ↓ | |||||||
| CD4+ T cells | = | ↓ | |||||||||||
| NK | ↓ | = | |||||||||||
| Tregs | ↓ | = | |||||||||||
| Immunomodulatory molecules | RNS/ROS | ↓ | |||||||||||
| iNOS | = | ||||||||||||
| Arginase-1 | ↑ (n.s.) | ↓ | ↓ | ↓ | |||||||||
| LAG3 | ↓ | ||||||||||||
| IL-6 | ↓ | ↓ (n.s.) | = | ||||||||||
| IL-10 | ↓ | ↓ (n.s.) | = | ||||||||||
| CTLA4 | ↓ | = | |||||||||||
| PDL1 | ↓ | = | |||||||||||
| TGF-β | = | = | = | ||||||||||
| IL-12 | = | ||||||||||||
| IFN-γ | = | ||||||||||||
| TNF-α | = | = | ↓ | ||||||||||
| Grazyme B | = | = | = | ||||||||||
| Perforin | = | = | = | ||||||||||
| Others4 | = | = | |||||||||||
| Spleen | Immune cell populations | Total MDSCs | ↓ | ↓ | ↓ (n.s.) | = | ↑ | ||||||
| MO-MDSC | = | ||||||||||||
| PMN-MDSCs | ↓ | ||||||||||||
| Macrophages | = | ||||||||||||
| CD8+ T cells | = | ↑ | ↓ | ||||||||||
| CD4+ T cells | = | ↑ | ↓ | ||||||||||
| NK | ↑ (n.s.) | = | |||||||||||
| Tregs | = | = | ↑ | ||||||||||
Data were obtained from Markiewski et al. [36], Corrales et al. [35], Nunez-Cruz et al.[59] and Gunn et al.[60]. The first three references correspond to models of complement inhibition. In contrast, the last study analyzed the effects of an increased expression of C5a (shaded boxes).
Cell lines inoculated in mice are indicated in parenthesis.
Abreviations: KO: knockout; AP: antagonist peptide; AA: antagonist antibody; Het.: heterozygous; MDSCs: myeloid-derived suppressor cells; MO: mononuclear; PMN: polymorphonuclear; Tregs: regulatory T cells; NK: natural killers; RNS: reactive nitrogen species; ROS: reactive oxygen species; n.s.: differences did not reach statistical significance; n.a.: statistical differences no available.
IDO, PD1, CCL17, CCL22, GITR, MCP1 and granzyme A.