Table 3. Classification of type II ICD inducers determined by their major targets to provoke antitumor responses.
| Anticancer agents | Type of cell death induced | DAMPs | Major targets by ICD inducers | Preclinical observations for inciting antitumor immunity |
|---|---|---|---|---|
| PDT with hypericin | Apoptosis, autophagic cell death dependent on Bax/Bak, necroptosis | Ecto-CRT, ecto-Hsp70, ectp-Hsp90, HMGB1, and ATP release | ER (ROS generation) | PDT -hypericin therapy provokes antitumor immunity in both prophylactic and therapeutic murine tumor models. Same therapy-treated tumor cells result in phenotypic maturation of DCs and robust CD4+T and CD8+T cell expansion |
| CVB3 | Apoptosis | Ecto-CRT, HMGB1 translocation, ATP release | ER (ROS generation) | Intratumoral CVB3 administration markedly recruited NK cells and granulocytes, both of which contribute to the antitumor effects as shown by depletion assays, macrophages, and mature DCs into tumor tissues |
| Ad5/3-hTERT-E1A-hCD40L: chimeric Ad5/3 capsid, an hTERT promoter and human CD40L | Apoptosis | Ecto-CRT, HMGB1 release, ATP release | ER (ROS generation) | In two syngeneic mouse models, murine CD40L induced activation of APCs, leading to increased IL-12 production in splenocytes, associated with induction of the Th1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells |
| Edmonston strain MV | Apoptosis | IL-6 production, HMGB1 release | ER (ROS generation) | Coculture of MV-infected melanoma cells with human DCs led to both CD80 and CD86 upregulation on them. CD8+ T cells cocultured with tumor cell-loaded and MV-infected DCs degranulated CD107a to target tumor cells with functional killing activity |
Abbreviations: PDT, photodynamic therapy; CVB3, coxasackievirus B3; MV, measles virus; ROS, reactive oxygen species; ER, endoplasmic reticulum; hTERT, telomerase reverse transcriptase; hCD40L, human CD40 ligand; Th1, T helper type 1; RANTES, regulated and normal T cell expressed and secreted; TNF-α, tumor necrosis factor-α IL-6, interleukin-6