Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential
Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed t...
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2023-06-01
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| Series: | Exploration of Targeted Anti-tumor Therapy |
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| Online Access: | https://www.explorationpub.com/Journals/etat/Article/1002146 |
| _version_ | 1797778318913699840 |
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| author | Eric Jou |
| author_facet | Eric Jou |
| author_sort | Eric Jou |
| collection | DOAJ |
| description | Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy. Type 1 immune cytokines, including interferon γ (IFNγ), interleukin-12 (IL-12), and tumour necrosis factor α (TNFα), have been shown to have largely tumour suppressive roles in part through orchestrating anti-tumour immune responses mediated by natural killer (NK) cells, CD8+ T cells and T helper 1 (Th1) cells. Conversely, type 2 immunity involving group 2 innate lymphoid cells (ILC2s) and Th2 cells are involved in tissue regeneration and wound repair and are traditionally thought to have pro-tumoural effects. However, it is found that the classical type 2 immune cytokines IL-4, IL-5, IL-9, and IL-13 may have conflicting roles in cancer. Similarly, type 2 immunity-related cytokines IL-25 and IL-33 with recently characterised roles in cancer may either promote or suppress tumorigenesis in a context-dependent manner. Furthermore, type 1 cytokines IFNγ and TNFα have also been found to have pro-tumoural effects under certain circumstances, further complicating the overall picture. Therefore, the dichotomy of type 1 and type 2 cytokines inhibiting and promoting tumours respectively is not concrete, and attempts of utilising these for cancer immunotherapy must take into account all available evidence. This review provides an overview summarising the current understanding of type 1 and type 2 cytokines in tumour immunity and discusses the prospects of harnessing these for immunotherapy in light of previous and ongoing clinical trials. |
| first_indexed | 2024-03-12T23:15:30Z |
| format | Article |
| id | doaj.art-87a5b386a6ef434283dab5c6f70c444e |
| institution | Directory Open Access Journal |
| issn | 2692-3114 |
| language | English |
| last_indexed | 2024-03-12T23:15:30Z |
| publishDate | 2023-06-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Targeted Anti-tumor Therapy |
| spelling | doaj.art-87a5b386a6ef434283dab5c6f70c444e2023-07-17T07:33:33ZengOpen Exploration Publishing Inc.Exploration of Targeted Anti-tumor Therapy2692-31142023-06-014347449710.37349/etat.2023.00146Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potentialEric Jou0https://orcid.org/0000-0002-6259-4874Queens’ College, University of Cambridge, CB3 9ET Cambridge, UK; MRC Laboratory of Molecular Biology, CB2 0QH Cambridge, UKCancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy. Type 1 immune cytokines, including interferon γ (IFNγ), interleukin-12 (IL-12), and tumour necrosis factor α (TNFα), have been shown to have largely tumour suppressive roles in part through orchestrating anti-tumour immune responses mediated by natural killer (NK) cells, CD8+ T cells and T helper 1 (Th1) cells. Conversely, type 2 immunity involving group 2 innate lymphoid cells (ILC2s) and Th2 cells are involved in tissue regeneration and wound repair and are traditionally thought to have pro-tumoural effects. However, it is found that the classical type 2 immune cytokines IL-4, IL-5, IL-9, and IL-13 may have conflicting roles in cancer. Similarly, type 2 immunity-related cytokines IL-25 and IL-33 with recently characterised roles in cancer may either promote or suppress tumorigenesis in a context-dependent manner. Furthermore, type 1 cytokines IFNγ and TNFα have also been found to have pro-tumoural effects under certain circumstances, further complicating the overall picture. Therefore, the dichotomy of type 1 and type 2 cytokines inhibiting and promoting tumours respectively is not concrete, and attempts of utilising these for cancer immunotherapy must take into account all available evidence. This review provides an overview summarising the current understanding of type 1 and type 2 cytokines in tumour immunity and discusses the prospects of harnessing these for immunotherapy in light of previous and ongoing clinical trials.https://www.explorationpub.com/Journals/etat/Article/1002146tumour microenvironmentcancer therapytargeted therapypreclinical modelsimmunotherapycytokinesoncology trials |
| spellingShingle | Eric Jou Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential Exploration of Targeted Anti-tumor Therapy tumour microenvironment cancer therapy targeted therapy preclinical models immunotherapy cytokines oncology trials |
| title | Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| title_full | Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| title_fullStr | Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| title_full_unstemmed | Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| title_short | Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| title_sort | type 1 and type 2 cytokine mediated immune orchestration in the tumour microenvironment and their therapeutic potential |
| topic | tumour microenvironment cancer therapy targeted therapy preclinical models immunotherapy cytokines oncology trials |
| url | https://www.explorationpub.com/Journals/etat/Article/1002146 |
| work_keys_str_mv | AT ericjou type1andtype2cytokinemediatedimmuneorchestrationinthetumourmicroenvironmentandtheirtherapeuticpotential |