Combination therapies with cytokines
| Sl. No. | Combination therapy | Cytokine used | Other therapy | Synergistic effect | Challenges | Reference |
|---|---|---|---|---|---|---|
| 1 | IL-2 and immune checkpoint inhibitors | IL-2 | PD-1/PD-L1 inhibitors | Enhance T cell activation | Severe immune-related toxicity | [63] |
| 2 | IFN-α with chemotherapy | IFN-α | Doxorubicin | Potentiates chemotherapy-induced tumor killing | Limited duration of response | [64] |
| 3 | TNF-α and radiotherapy | TNF-α | Localized radiation | Synergizes with radiation-induced cell death | Local tissue damage | [65] |
| 4 | IL-12 and IL-2 | IL-12, IL-2 | Dual cytokine therapy | Amplifies antitumor immune response | Cytokine release syndrome | [66] |
| 5 | IL-6 inhibition and chemotherapy | IL-6 antagonists | Cisplatin | Reduces chemotherapy resistance | Potential for exacerbating infection risks | [67] |
| 6 | IL-15 and NK cell adoptive transfer | IL-15 | NK cell therapy | Enhances NK cell cytotoxicity | Cytokine-related toxicity | [50] |
| 7 | IL-10 blockade with PD-1 inhibitors | Anti-IL-10 | PD-1/PD-L1 inhibitors | Reverses immune suppression in TME | Increased risk of autoimmune diseases | [68] |
| 8 | TGF-β inhibitors and VEGF inhibitors | TGF-β inhibitors | Anti-angiogenic agents | Reduces tumor vasculature | Potential for severe adverse vascular events | [69] |
| 9 | IL-1 blockades with radiotherapy | IL-1 antagonists | Radiation | Reduces tumor recurrence | Immunosuppressive side effects | [70] |
| 10 | IL-22 inhibition and checkpoint inhibitors | IL-22 inhibitors | PD-1/PD-L1 inhibitors | Overcomes immune evasion | Off-target effects on normal tissue | [71] |
| 11 | GM-CSF and cancer vaccines | GM-CSF | Peptide-based vaccines | Enhances vaccine efficacy | Inconsistent results across patient populations | [72] |
| 12 | IL-18 and chemotherapy | IL-18 | Paclitaxel | Enhances chemotherapy-induced apoptosis | Severe cytokine-related toxicity | [73] |
| 13 | IL-2 and adoptive T cell therapy | IL-2 | CAR-T therapy | Amplifies CAR-T cell efficacy | High toxicity and cytokine release syndrome | [74] |
| 14 | IFN-γ with oncolytic viruses | IFN-γ | Oncolytic viral therapy | Enhances viral-induced tumor cell death | High inflammatory response | [75] |
| 15 | TGF-β blockade with chemotherapy | TGF-β inhibitors | Cisplatin | Inhibits tumor progression and metastasis | Risk of systemic toxicity | [76] |
IL-2: interleukin-2; IFN-α: interferon-alpha; TNF-α: tumor necrosis factor-alpha; NK: natural killer; TME: tumor microenvironment; TGF-β: transforming growth factor-beta
The authors are thankful to their parent institutions for their continued support, resources, and encouragement throughout this research. Their infrastructural and administrative assistance was instrumental in the successful completion of this work.
MMCM: Conceptualization, Writing—original draft. BSB: Writing—original draft, Writing—review & editing. VAS: Supervision, Conceptualization, Validation. SA: Writing—review & editing. HC: Supervision, Conceptualization, Validation.
The authors declare that they have no conflicts of interest.
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