|
| CHS immune cell | CHS immune reaction | Plausible direct and indirect mechanisms of tumor regression |
|
| Hapten modification of epidermal cells → release of danger signals | ATP release → P2RX7 → NLRP3 activation | IL-18 and IL-1β → protection against colorectal tumorigenesis [115] |
| ROS | Inhibit MDSC maturation [116] |
| Induce cell death in established tumor [117] |
|
| Dermal APCs | Stimulation by haptenization | Possibly stimulate exhausted CD8+ T-cells [118, 119] |
|
| Keratinocytes | IL-18 release | Protection against colorectal tumorigenesis [116] |
| IL-1β release | Polarization of IFNγ CD8+ T-cells [115] |
|
| iNKT cells | IFNγ production | Protective role dependent on Th1 cytokines [140] and antitumor activity [150] |
|
| Mast cells | TNFα and CXCL2 release | Neutrophil activation [4] |
| TNFα and serotonin release | Chemokine, selectin and adhesion molecule upregulation for hapten-specific T-cell trafficking |
|
| Neutrophils | KC damage (FasL and perforin) | Potential tumor damage, although neutrophils not known to directly kill tumor cells in the first 24 hours [121, 122] |
| CXCL1 and CXCL2 | Chemokine, selectin and adhesion molecule upregulation for hapten-specific T-cell trafficking |
|
| CS initiating B-1 cells | Hapten-antibody production | Hapten-tumor IgM → ADCC |
|
| CD8+ T-cells | IFNγ | TIL activation [125] and antitumor activity [150] |
| Hapten-specific CD8+ T-cells | Haptenated-tumor cell killing |
| Infiltration into CHS site | Tumor-infiltrating lymphocytes [125] |
|
| CD4+ T-cells | Hapten-specific | Rescue exhausted CD8+ T-cells [123] |
|
| Tc17/Th17 | IL-17 CD4+ and CD8+ Cells | Antitumor immune responses [126, 127] |
|
| Hepatic NK cells | Hapten-specific NK-cells | Hapten-tumor cell killing [128] |
|
