Table 2.
Immunotherapy strategy for pancreatic cancer based on tumor microenvironment.
| Intervention | Strategy | Cancer stage | Trials/Identifier | Outcomes & response | Ref. |
|---|---|---|---|---|---|
| ICI | |||||
| Ipilimumab | CTLA-4 antibody | Advanced PC | Ib | Gemcitabine and ipilimumab is a safe regimen with tolerable adverse events | (123) |
| Pembrolizumab | PD-1 antibody | Metastatic PC | I/II NCT02331251 | Combining pembrolizumab with gemcitabine and nab-paclitaxel chemotherapy improve the prognosis. | (124) |
| Tremelimumab | CTLA-4 antibody | Metastatic PC | I/ NCT00556023 | The median OS was 7.4 months (95% CI 5.8-9.4 months) by combing tremelimumab plus gemcitabine with tolerable toxicities | (125) |
| Tremelimumab | CTLA-4 antibody | Metastatic PC | II/NCT02527434 | The efficacy of tremelimumab as monotherapy was unsatisfactory with a poor prognosis | (126) |
| Targeting TME | |||||
| Galunisertib | TβRI kinase inhibitor | Unresectable PC | 1b/II | Galunisertib combining with gemcitabine improve the OS and PFS | (127) |
| Galunisertib | TβRI kinase inhibitor | Metastatic PC | Ib /NCT02734160 | Combining galunisertib with durvalumab achieved a DCR of 25.0% and a confirmed ORR of 3.1% | (128) |
| PECPH20 | Intratumoural pressure | Animals models | Preclinical studies | PECPH20 combined with chemotherapeutic drugs decrease tumor volume and improve OS | (129) |
| PECPH20 | Intratumoural pressure | Metastatic PC | IB/II | This combination of PECPH20 with FOLFIRINOX caused increased toxicity with shortened OS. | (130) |
| PECPH20 | Intratumoural pressure | IV PC | Ib | OS and PFS were not improved in patients treated with PECPH20 combined with paclitaxel and gemcitabine | (131) |
| Bruton tyrosine kinase inhibitor | MDSCs | Metastatic or locally advanced PC | II | The combination of acalabrutinib and pembrolizumab was well tolerated with disappointing ORR and DCR | (132) |
| INF-2α | IFN-γ and IL-10 | Resected PC | NP | INF-2α promoted the DCs and NK cells activation | (133) |
| IL-6 | Targeting myeloid progenitor cells and B and T lymphocytes | Advanced PC and colon cancer | I | Induction of CRP and IgE; inhibition of NK and lymphokine-activated killer cell activity | (134) |
| BL-8040 | CXCR4 antagonist | metastatic PC | NCT02826486 | Combined BL-8040 and pembrolizumab improved the effect of chemotherapy | (135) |
| Cancer vaccination | |||||
| DC vaccination | MUC1 peptide-loaded DCs | Metastatic PC positive for MUC1 | I | The MUC1-peptide-pulsed DCs was non-toxic and capable of inducing immunological response | (136) |
| DC vaccination | MUC1 peptide-loaded DCs | Unresectable or recurrent PC | MUC1-DC was feasible and effective with tolerable toxicity | (137) | |
| DC vaccination | MUC1 peptide-loaded DCs | Resected PC | I/II | The median survival is 26 months (range 13-69 months) for all patients with | (138) |
| DC vaccination | DC/WT1-I/II | IV PC | I | The DC/WT1-I/II combined with chemotherapy effectively activated WT1-specific immune responses and promoted disease stability | (139) |
| DC vaccination | Poly-ICLC to peptide-pulsed DCs | Advanced PC | NCT01410968 | DCs loaded with poly-ICLC is safe and induces a measurable tumor specific T cell population | (140) |
| NK cells | Irreversible electroporation (IRE) | Metastatic PC | NCT02718859 | Combining NK cells with IRE had a synergistic effect with satisfactory short-term outcome | (141) |
| NK cells | (IRE) | III/IV PC | NP | Combining NK cells with IRE significantly extended PFS and OS | (142) |
| Lenalidomide | NK cells | Advanced PC | NCT01547260 | Lenalidomide augmented a significant increase in the numbers of CD4+ and CD8+ T cells | (143) |
| KWAR23 | SIRP α monoclonal antibody | Solid tumors | NP | Enhancing myeloid cell-dependent tumor killing ability, activates neutrophils and macrophages, and inhibits tumor growth | (144) |
| Extracellular vesicles (EVs) | |||||
| Exosomes from fibroblast-like mesenchymal cells | siRNA specific to oncogenic KrasG12D | Animals models | NA | The engineered exosomes suppressed cancer growth and significantly improved overall survival | (145) |
| Exosomes from HEK293T cells | Inhibitor of interaction between CD47 and SIRPα | Animals models | NA | promoting an intensive T cell infiltration and inhibiting tumor growth | (146) |
| Exosomes from tumor cells | Containing tumor antigens and immunostimulatory CpG DNA | Animals models | NA | Enhancing tumor antigen presentation capacity and antitumor effects of DCs | (147) |
| Exosomes from myeloma cell | Containing HSP70 and P1A tumor antigen | Animals models | NA | Promoting CTL responses and antitumour immunity | (148) |
| Exosomes from DCs | Delivering antigen and costimulatory molecules | Animals models | NA | Stimulating cytotoxic T lymphocytes and inducing efficient antitumor immunity | (149) |
| Exosomes from DCs | Delivering antigen and costimulatory molecules | IIIb and IV non-small cell lung cancer | I | Activating immune effectors and having long term stability of disease | (150) |
| EVs from CD8+ T cell | Targeting lesional mesenchymal cell | Animals models | NA | Preventing tumor progressions | (151) |
| Exosomes from NK cells | Expressing FasL and perforin | In vitro experiment | NA | Exerting a cytotoxic activity against target cells | (152) |
| Exosomes from M1-macrophages | Delivering proinflammatory signal to produce more Th1 cytokines | Animals models | NA | Inducing a stronger antigen-specific cytotoxic T cell response | (153) |