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Research Developments in Cancer Hallmarks and Immune Checkpoints Based on Mechanisms of Tumour Microenvironment
- 1 Singapore International School (Hong Kong), Hong Kong, China
* Author to whom correspondence should be addressed.
Abstract
Cancer has been one of the most concerning diseases around the globe, and oncologists have been developing different insightful therapies in the last century. With the shifted focus on immunotherapy, analysing the tumour microenvironment (TME) is crucial for cancer hallmark identification and subsequent antibody-based inhibition. Currently, PD-1/PD-L1 and CTLA-4 immune checkpoints are studied intensively, and there are FDA-approved immune checkpoint inhibitors (ICIs) such as Ipilimumab for anti-CTLA-4. Also, the characteristics of TMEs are expanded to include genomic instability and epigenetic factors. However, the complexities of TMEs disallow oncologists to consider all aspects, and tackling immune checkpoints can lead to unintended consequences. Therefore, this review report aims to investigate the common biochemicals and immune responses within TMEs, and how different types of TMEs have different overexpressions. Based on the chemical interactions in TME, the targetable cancer hallmarks will be investigated, with an inclination toward the fast-growing immune checkpoint inhibitors. It is concluded that cytokine-induced inflammation in TME causes Treg responses and immune escape by tumour cells, which can be categorised into different types. Also, immune checkpoint inhibitors show promising results against solid or liquid tumours when used in the right conditions. Overall, this report emphasises the diversity and informs the key characteristics of TMEs; it reminds the medical field that immune checkpoint inhibitors may not always bring a better prognosis. A thorough understanding of TME is important for future research developments. In the future, there could be more focus on combination therapies on immune checkpoints
Keywords
immune checkpoint, tumour microenvironment, CTLA-4, PD-1/PD-L1
[1]. Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), 17–48.
[2]. Zhao, H., Wu, L., Yan, G., et al. (2021). Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduction and Targeted Therapy, 6, 263.
[3]. Li, C., Jiang, P., Wei, S., Xu, X., & Wang, J. (2020). Regulatory T cells in tumor microenvironment: New mechanisms, potential therapeutic strategies and future prospects. Molecular Cancer, 19(1), Article 1234.
[4]. Blunt, M. D., & Khakoo, S. I. (2023). Harnessing natural killer cell effector function against cancer. OUP Academic.
[5]. Xu, X., Sun, Q., Liang, X., Chen, Z., Zhang, X., Zhou, X., Li, M., Tu, H., Liu, Y., Tu, S., & Li, Y. (2019). Mechanisms of relapse after CD19 CAR T-cell therapy for acute lymphoblastic leukemia and its prevention and treatment strategies. Frontiers in Immunology, 10.
[6]. Yang, H., Zhang, Z., Li, J., Wang, K., Zhu, W., & Zeng, Y. (2024). The dual role of B cells in the tumor microenvironment: Implications for cancer immunology and therapy. Molecules, 25(21), Article 11825.
[7]. Falcomatà, C., Bärthel, S., Schneider, G., Rad, R., Schmidt-Supprian, M., & Saur, D. (2023). Context-specific determinants of the immunosuppressive tumor microenvironment in pancreatic cancer. Cancer Discovery, 13(2), 278–297.
[8]. EG;, B. S. R. (2022). Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annual Review of Pathology.
[9]. Rašková, M., Lacina, L., Kejík, Z., Venhauerová, A., Skaličková, M., Kolář, M., Jakubek, M., Rosel, D., Smetana, K., & Brábek, J. (2022). The role of IL-6 in cancer cell invasiveness and metastasis—Overview and therapeutic opportunities. Cells, 11(22), Article 3698.
[10]. Matsushima, K., Yang, D., & Oppenheim, J. J. (2022). Interleukin-8: An evolving chemokine. Cytokine, 153, Article 155828.
[11]. Deng, Z., Fan, T., Xiao, C., Tian, H., Zheng, Y., Li, C., & He, J. (2024). TGF-β signaling in health, disease and therapeutics. Nature News.
[12]. Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022). Combination strategies with PD-1/PD-L1 blockade: Current advances and future directions. Molecular Cancer, 21(1), Article 28.
[13]. Tan, Z., Xue, H., Sun, Y., Zhang, C., Song, Y., & Qi, Y. (2021). The role of tumor inflammatory microenvironment in lung cancer. Frontiers in Pharmacology, 12.
[14]. Zeltz C., Primac I., Erusappan P., Alam J., Noel A., & Gullberg D. (2020). Cancer-associated fibroblasts in desmoplastic tumors: Emerging role of integrins. In Seminars in Cancer Biology (Vol. 62 pp. 166-181).
[15]. Chen G., Wu K., Li H., Xia D., & He T., (2022). Role of hypoxia in the tumor microenvironment and targeted therapy. Frontiers in Oncology, 12.
[16]. Bonilla D.L., Reinin G., & Chua E., (2021). Full spectrum flow cytometry as a powerful technology for cancer immunotherapy research. Frontiers in Molecular Biosciences, 7.
[17]. Simonetti S., Natalini A., Peruzzi G., Nicosia A., Folgori A., Capone S. & Di Rosa F., (2021). A DNA/Ki67-based flow cytometry assay for cell cycle analysis of antigen-specific CD8 T cells in vaccinated mice.Journal of Visualized Experiments, 167.
[18]. Warren C.F., Wong-Brown M.W., & Bowden N.A., (2019). BCL-2 family isoforms in apoptosis and cancer. Cell Death & Disease, 10(3), Article 177.
[19]. Liu L.L., Skribek M., Harmenberg U., & Gerling M., (2023). Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Case report and systematic review of the literature.Journal for ImmunoTherapy of Cancer, 11(3), Article e005841.
Cite this article
Jin,C. (2025). Research Developments in Cancer Hallmarks and Immune Checkpoints Based on Mechanisms of Tumour Microenvironment. Theoretical and Natural Science,90,38-47.
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Volume title: Proceedings of ICMMGH 2025 Workshop: Computational Modelling in Biology and Medicine
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