Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India.
Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India; Centre for Cancer Research, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India.
Int Immunopharmacol. 2024 Oct 25;140:112837. doi: 10.1016/j.intimp.2024.112837. Epub 2024 Aug 6.
Propensity to develop cervical cancer (CC) in human papilloma virus (HPV) infected individual could potentially involve the impaired immune functioning. Several stages of HPV surveillance by immune cells in tumor micro-environment (TME) is regulated mainly by transforming growth factor-beta (TGF-β) and is crucial for the establishment of CC. The role of TGF-β in the initiation and progression of CC is very complex and involve different suppressor of mothers against decapentaplegic homolog (SMAD) dependent and SMAD independent signaling mechanism(s). This review summarizes the handling of HPV by immune cells such as T lymphocytes, B lymphocytes, natural killer cells (NK), dendritic cells (DC), monocytes, macrophages, myeloid derived suppressor cells (MDSC) and their regulation by TGF-β. The hijack mechanisms adapted by HPV to evade this surveillance process is discussed. Biomarkers indicating the stages of CC and immune checkpoints that can be targeted for improved outcome are included for immune-based theragnostics. This review also addresses the direct actions of TGF-β on CC cells and tumor/immune cell interactions. Therapies focused on targeting TGF-β using small molecule inhibitors, monoclonal antibodies and TGF-β chimeric antigen receptor (CAR)T cells are collated to understand the current strategies related to TGF-β in the management of CC.
人乳头瘤病毒（HPV）感染个体发展宫颈癌（CC）的倾向可能涉及免疫功能受损。免疫细胞在肿瘤微环境（TME）中对 HPV 的几个监测阶段主要受转化生长因子-β（TGF-β）调节，这对于 CC 的建立至关重要。TGF-β 在 CC 的发生和进展中的作用非常复杂，涉及不同的母亲对抗 decapentaplegic 同源物（SMAD）的抑制因子（SMAD）依赖性和 SMAD 非依赖性信号机制。这篇综述总结了免疫细胞（如 T 淋巴细胞、B 淋巴细胞、自然杀伤细胞（NK）、树突状细胞（DC）、单核细胞、巨噬细胞、髓源性抑制细胞（MDSC））对 HPV 的处理及其受 TGF-β的调节。讨论了 HPV 为逃避这种监测过程而采用的劫持机制。包括用于免疫治疗的表明 CC 阶段的生物标志物和可以作为靶点以改善结果的免疫检查点。这篇综述还涉及 TGF-β对 CC 细胞和肿瘤/免疫细胞相互作用的直接作用。综述了集中于使用小分子抑制剂、单克隆抗体和 TGF-β嵌合抗原受体（CAR）T 细胞靶向 TGF-β的疗法，以了解与 TGF-β在 CC 管理相关的当前策略。
