Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul, South Korea.
YbdYbiotech Research Center, Seoul, South Korea.
Front Immunol. 2022 Feb 25;13:837590. doi: 10.3389/fimmu.2022.837590. eCollection 2022.
IL-32 plays a contradictory role such as tumor proliferation or suppressor in cancer development depending on the cancer type. In most cancers, it was found that the high expression of IL-32 was associated with more proliferative and progression of cancer. However, studying the isoforms of IL-32 cytokine has placed its paradoxical role into a wide range of functions based on its dominant isoform and surrounding environment. IL-32β, for example, was found mostly in different types of cancer and associated with cancer expansion. This observation is legitimate since cancer exhibits some hypoxic environment and IL-32β was known to be induced under hypoxic conditions. However, IL-32θ interacts directly with protein kinase C-δ reducing NF-κB and STAT3 levels to inhibit epithelial-mesenchymal transition (EMT). This effect could explain the different functions of IL-32 isoforms in cancer. However, pro- or antitumor activity which is dependant on obesity, gender, and age as it relates to IL-32 has yet to be studied. Obesity-related IL-32 regulation indicated the role of IL-32 in cancer metabolism and inflammation. IL-32-specific direction in cancer therapy is difficult to conclude. In this review, we address that the paradoxical effect of IL-32 on cancer is attributed to the dominant isoform, cancer type, tumor microenvironment, and genetic background. IL-32 seems to have a contradictory role in cancer. However, investigating multiple IL-32 isoforms could explain this doubt and bring us closer to using them in therapy.
IL-32 在癌症发展中扮演着矛盾的角色，例如在某些癌症中促进肿瘤增殖，而在另一些癌症中则起到抑制作用。在大多数癌症中，发现 IL-32 的高表达与癌症的增殖和进展更为相关。然而，研究 IL-32 细胞因子的同工型将其矛盾的作用置于广泛的功能范围内，这取决于其优势同工型和周围环境。例如，IL-32β 主要存在于不同类型的癌症中，并与癌症的扩张有关。这种观察是合理的，因为癌症表现出一些缺氧环境，而 IL-32β 已知在缺氧条件下被诱导。然而，IL-32θ 与蛋白激酶 C-δ直接相互作用，降低 NF-κB 和 STAT3 水平，从而抑制上皮-间充质转化（EMT）。这种效应可以解释 IL-32 同工型在癌症中的不同功能。然而，依赖于肥胖、性别和年龄的促癌或抑癌活性与 IL-32 相关，尚未得到研究。肥胖相关的 IL-32 调节表明 IL-32 在癌症代谢和炎症中的作用。IL-32 特异性在癌症治疗中的方向难以得出结论。在这篇综述中，我们认为 IL-32 对癌症的矛盾作用归因于优势同工型、癌症类型、肿瘤微环境和遗传背景。IL-32 在癌症中似乎扮演着矛盾的角色。然而，研究多个 IL-32 同工型可以解释这种疑问，并使我们更接近于在治疗中使用它们。
