Journal of Cell Science & Therapy
Open Access

The Role of Cytokines in Cancer Progression and Therapy

Riya Haines^{* *}Correspondence: Riya Haines, Department of Oncology, University of Guelph, Guelph, Canada, Email:

Author info »

Description

Cytokines are essential signaling molecules that orchestrate a wide array of physiological processes, including immune responses and inflammation. Their roles in cancer are complex and multifaceted, influencing both tumor progression and therapeutic strategies. The role of cytokines in cancer progression and therapy, exploring their dualistic nature as both facilitators and targets in the battle against cancer.

Cytokines

Cytokines are small proteins released by cells that affect the behaviour of other cells. They function through specific receptors on target cells and can influence a range of processes, including cell proliferation, differentiation and apoptosis. Key cytokines involved in cancer include interleukins, Tumour Necrosis Factors (TNFs), interferons and growth factors [1].

Cytokines and cancer progression

Cytokines can both promote and inhibit cancer progression. Their effects on tumor biology are influenced by the type of cytokine, the stage of cancer and the tumor microenvironment.

Pro-tumorigenic cytokines: IL-6 is a key player in inflammation and is often found at elevated levels in various cancers, including breast, prostate and colorectal cancers. It promotes tumorigenesis by activating the STAT3 signaling pathway, which enhances cell proliferation, survival and angiogenesis. TNF-α is involved in systemic inflammation and can have dual effects depending on its context. While it has the potential to induce apoptosis in cancer cells, chronic exposure to TNF-α can lead to the development of drug resistance, increased tumor growth and enhanced metastatic potential [2-5].

Anti-tumorigenic cytokines: Interferons (IFN), particularly IFN-α and IFN-β, have anti-tumor effects through their ability to enhance immune surveillance and directly inhibit tumor cell proliferation [6]. They induce the expression of Major Histocompatibility Complex (MHC) molecules, facilitating the recognition of tumor cells by Cytotoxic T Lymphocytes (CTLs). IL-2 is known for its role in promoting the growth and activation of T cells. In the context of cancer therapy, high-dose IL-2 has been used to stimulate the immune system against tumors, particularly in melanoma and renal cell carcinoma [7-9].

Cytokine based therapies

Recombinant cytokines, such as recombinant IL-2 and IFN-α, have been used to boost the immune response against tumors. While they can be effective, their use is often limited by toxicity and the development of resistance. Advances in understanding cytokine biology are leading to improved formulations and combination therapies to enhance efficacy and minimize side effects. Targeting cytokine receptors with agonists or antagonists can modulate the effects of cytokines in the tumor microenvironment [10].

Immunotherapy and cytokines

Immunotherapy harnesses the body’s immune system to target and destroy cancer cells. Cytokines play an important role in this strategy.

Chimeric Antigen Receptor (CAR) T-cell therapy: CAR T-cell therapy involves engineering patient’s T cells to express receptors specific to tumor antigens. Cytokines such as IL-12 are used to enhance the efficacy of CAR T-cell therapy by boosting T-cell activation and persistence [11].

Checkpoint inhibitors: Checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, are designed to block the inhibitory signals that cancer cells use to evade immune surveillance. While these therapies primarily target immune checkpoints, cytokines play a role in modulating the immune response and influencing treatment outcomes [12].

Conclusion

Cytokines play a vital role in cancer progression and therapy, acting as both facilitators and targets in the complex landscape of cancer treatment. While their dualistic nature presents challenges, ongoing research and technological advancements are creating foundation for innovative therapies that leverage the power of cytokines to improve patient outcomes. As our understanding of cytokine biology deepens, the potential for more effective and targeted cancer treatments.

References

1. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4(1):11-22.

   [Crossref] [Google Scholar] [PubMed]

2. Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19(4):237-253.

   [Crossref] [Google Scholar] [PubMed]

3. Qiu Y, Su M, Liu L, Tang Y, Pan Y, Sun J. Clinical application of cytokines in cancer immunotherapy. Drug Des Devel Ther. 2021;27:2269-2287.

   [Crossref] [Google Scholar] [PubMed]

4. Lan T, Chen L, Wei X. Inflammatory cytokines in cancer: comprehensive understanding and clinical progress in gene therapy. Cells. 2021;10(1):100.

   [Crossref] [Google Scholar] [PubMed]

5. Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, Pérez-Gracia JL, et al. Cytokines in clinical cancer immunotherapy. Br J Cancer. 2019;120(1):6-15.

   [Crossref] [Google Scholar] [PubMed]

6. Borden EC, Sondel PM. Lymphokines and cytokines as cancer treatment. Immunotherapy realized. Cancer. 1990;65(S3):800-814.

   [Crossref] [Google Scholar] [PubMed]

7. Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y. Cytokines in cancer immunity and immunotherapy. Immunol. Rev. 2004;202(1):275-293.

   [Crossref] [Google Scholar] [PubMed]

8. Xue D, Hsu E, Fu YX, Peng H. Next-generation cytokines for cancer immunotherapy. Antib Ther. 2021;4(2):123-133.

   [Crossref] [Google Scholar] [PubMed]

9. Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, et al. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett. 2020; 470:126-133.

   [Crossref] [Google Scholar] [PubMed]

10. Jiang GM, Tan Y, Wang H, Peng L, Chen HT, Meng XJ, et al. The relationship between autophagy and the immune system and its applications for tumor immunotherapy. Mol Cancer. 2019;18:1-22.

    [Crossref] [Google Scholar] [PubMed]

11. Devaud C, John LB, Westwood JA, Darcy PK, Kershaw MH. Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy. Oncoimmunology. 2013;2(8):e25961.

    [Crossref] [Google Scholar] [PubMed]

12. Vasievich EA, Huang L. The suppressive tumor microenvironment: A challenge in cancer immunotherapy. Mol Pharmaceutics. 2011;8(3):635-641.

    [Crossref] [Google Scholar] [PubMed]