Cytokines, a class of soluble proteins that are key mediators of cell communication in the tumour microenvironment (TME), can regulate both innate and adaptive immunity. Tumour-related cytokines, especially pro-inflammatory cytokines (such as TNF, IL-6, and IL-1), have a well-recognized tumour-promoting activity and take part in the various phases of tumour initiation and progression. Furthermore, some of them even can promote or aggravate tumour progression during tumour therapy, reducing the efficacy of anti-tumour drugs. For example, tumour-derived IL-35 enhances the secretion of IL-6 and G-CSF, inhibits the production of IFN-?, and suppresses tumour-infiltrating lymphocytes (TILs) infiltration and effector cell proliferation, promoting tumour growth, progression, and metastasis. TGF-ß promotes CD8+ T cell exhaustion and attenuates tumour response to PD-L1 blockade. IL-6 suppresses chemotherapy-induced anti-cancer immunity and reduces the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. In addition, although some effector cytokines, such as FDA-approved IL-2 and IFN-a and clinically-evaluated IL-12 and IL-10, have attracted extensive attention from researchers in cytokine therapy. However, their adverse effects resulting from the complexity of the cytokine network during anti-tumour immunity may contribute to the metastasis and growth of aggressive tumour cells through immunosuppression and TME modulation. For example, IL-2 can induce the expression of immune checkpoint molecules CTLA-4, PD-1, and PD-1 ligands PD-L1. IL-10 inhibits the immune response and regulates the generation and infiltration of Treg cells, leading to the escape of the tumour cells from immunosurveillance.
Given the negative roles of cytokines in tumour therapy, these cytokines or related receptors are becoming attractive candidates for tumour-targeted therapies, with a great potential for wide application. Therefore, the research on the tumour-promoting effect of cytokines will play a key role in further revealing the molecular mechanisms of tumour development and identifying novel therapeutic targets for tumour therapy.
In this research topic, we aim to provide a comprehensive overview of recent progress in the negative roles that cytokines played in tumour therapy and how to circumvent these impediments from basic research to clinical applications. We are specifically interested in the signalling pathways that regulate the release of these cytokines and the molecular mechanisms by which these cytokines play a negative role in tumour therapy.
We welcome the submission of Original Research articles, Reviews, and Mini-Reviews covering the following subtopics:
(1) Novel cytokines that affect tumour therapy and promote tumorigenesis, and the mechanisms of their tumour-promoting effect;
(2) Novel mechanisms underlying known cytokines exacerbating tumorigenesis during tumour therapy;
(3) Novel therapeutic agents that block the tumour-promoting activities of cytokines, including antagonistic antibodies, small molecules, cytokine traps or siRNAs;
(4) New approaches employed to improve the anti-tumour activity of cytokine therapy, for example, the combination of cytokines with immune checkpoint inhibitors (e.g., IL-2 and nivolumab, IL-10 and pembrolizumab) or other immunotherapies (e.g., CAR T cell therapy) and/or the modification of cytokines (e.g., IL-2 ‘superkines’ and the IL-12 immune-cytokines);
(5) Innovative strategies based on computational research to generate new reagents targeting cytokines, or to identify the new cytokines candidates to be targeted.
Cytokines, a class of soluble proteins that are key mediators of cell communication in the tumour microenvironment (TME), can regulate both innate and adaptive immunity. Tumour-related cytokines, especially pro-inflammatory cytokines (such as TNF, IL-6, and IL-1), have a well-recognized tumour-promoting activity and take part in the various phases of tumour initiation and progression. Furthermore, some of them even can promote or aggravate tumour progression during tumour therapy, reducing the efficacy of anti-tumour drugs. For example, tumour-derived IL-35 enhances the secretion of IL-6 and G-CSF, inhibits the production of IFN-?, and suppresses tumour-infiltrating lymphocytes (TILs) infiltration and effector cell proliferation, promoting tumour growth, progression, and metastasis. TGF-ß promotes CD8+ T cell exhaustion and attenuates tumour response to PD-L1 blockade. IL-6 suppresses chemotherapy-induced anti-cancer immunity and reduces the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. In addition, although some effector cytokines, such as FDA-approved IL-2 and IFN-a and clinically-evaluated IL-12 and IL-10, have attracted extensive attention from researchers in cytokine therapy. However, their adverse effects resulting from the complexity of the cytokine network during anti-tumour immunity may contribute to the metastasis and growth of aggressive tumour cells through immunosuppression and TME modulation. For example, IL-2 can induce the expression of immune checkpoint molecules CTLA-4, PD-1, and PD-1 ligands PD-L1. IL-10 inhibits the immune response and regulates the generation and infiltration of Treg cells, leading to the escape of the tumour cells from immunosurveillance.
Given the negative roles of cytokines in tumour therapy, these cytokines or related receptors are becoming attractive candidates for tumour-targeted therapies, with a great potential for wide application. Therefore, the research on the tumour-promoting effect of cytokines will play a key role in further revealing the molecular mechanisms of tumour development and identifying novel therapeutic targets for tumour therapy.
In this research topic, we aim to provide a comprehensive overview of recent progress in the negative roles that cytokines played in tumour therapy and how to circumvent these impediments from basic research to clinical applications. We are specifically interested in the signalling pathways that regulate the release of these cytokines and the molecular mechanisms by which these cytokines play a negative role in tumour therapy.
We welcome the submission of Original Research articles, Reviews, and Mini-Reviews covering the following subtopics:
(1) Novel cytokines that affect tumour therapy and promote tumorigenesis, and the mechanisms of their tumour-promoting effect;
(2) Novel mechanisms underlying known cytokines exacerbating tumorigenesis during tumour therapy;
(3) Novel therapeutic agents that block the tumour-promoting activities of cytokines, including antagonistic antibodies, small molecules, cytokine traps or siRNAs;
(4) New approaches employed to improve the anti-tumour activity of cytokine therapy, for example, the combination of cytokines with immune checkpoint inhibitors (e.g., IL-2 and nivolumab, IL-10 and pembrolizumab) or other immunotherapies (e.g., CAR T cell therapy) and/or the modification of cytokines (e.g., IL-2 ‘superkines’ and the IL-12 immune-cytokines);
(5) Innovative strategies based on computational research to generate new reagents targeting cytokines, or to identify the new cytokines candidates to be targeted.