Jasemi Seyedesomaye, Simula Elena Rita, Lin Yao, Satta Rosanna Rita, Rubino Corrado, Cossu Antonio, Fais Milena, Noli Marta, Sechi Leonardo A
Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy.
Department of Medicine and Pharmacy, University of Sassari, 07100 Sassari, Italy.
Cancers (Basel). 2025 Aug 23;17(17):2737. doi: 10.3390/cancers17172737.
Despite notable progress in cancer therapy, immune evasion remains a major obstacle to effective treatment outcomes. In the context of spaceflight, astronauts are exposed to unique environmental stressors-particularly microgravity and radiation-that profoundly affect cellular and immune homeostasis. Emerging evidence suggests that microgravity alters key cellular processes, including proliferation, apoptosis, adhesion, and oncogenic signaling pathways such as NF-κB and ERK1/2. Concurrently, microgravity (µg) disrupts immune regulation, potentially facilitating both tumor progression and treatment resistance. Of particular concern is the upregulation of human endogenous retroviruses (HERVs), especially HERV-K and HERV-W, under µg conditions, which may exacerbate inflammatory responses and immune system dysregulation. While some studies indicate that µg may impair tumor growth, others reveal enhanced immune evasion and reduced antitumor immunity. Importantly, insights from µg research extend beyond space medicine and provide translational opportunities for terrestrial oncology, including the development of physiologically relevant 3D tumor models for drug screening, the identification of mechano-sensitive pathways (FAK/RhoA, YAP/TAZ) as therapeutic targets, and novel immunotherapeutic strategies involving epigenetic modulation and checkpoint inhibition. This review critically examines the dual role of µg in modulating cancer progression and immune function. We synthesize findings on how µg shapes immune responses, alters tumor-immune system interactions, and impacts the efficacy of immunotherapeutic approaches. Finally, we highlight translational opportunities and challenges for optimizing cancer immunotherapy and precision oncology in both spaceflight and Earth-based environments.
尽管癌症治疗取得了显著进展，但免疫逃逸仍然是有效治疗结果的主要障碍。在太空飞行的背景下，宇航员面临着独特的环境压力源，特别是微重力和辐射，这些因素会深刻影响细胞和免疫稳态。新出现的证据表明，微重力会改变关键的细胞过程，包括增殖、凋亡、黏附以及诸如NF-κB和ERK1/2等致癌信号通路。同时，微重力会破坏免疫调节，可能促进肿瘤进展和治疗抗性。特别值得关注的是，在微重力条件下人类内源性逆转录病毒（HERV），尤其是HERV-K和HERV-W的上调，这可能会加剧炎症反应和免疫系统失调。虽然一些研究表明微重力可能会损害肿瘤生长，但其他研究则显示免疫逃逸增强和抗肿瘤免疫力降低。重要的是，微重力研究的见解不仅限于太空医学，还为地面肿瘤学提供了转化机会，包括开发用于药物筛选的生理相关3D肿瘤模型、将机械敏感通路（FAK/RhoA、YAP/TAZ）鉴定为治疗靶点，以及涉及表观遗传调节和检查点抑制的新型免疫治疗策略。本综述批判性地审视了微重力在调节癌症进展和免疫功能方面的双重作用。我们综合了关于微重力如何塑造免疫反应、改变肿瘤-免疫系统相互作用以及影响免疫治疗方法疗效的研究结果。最后，我们强调了在太空飞行和地面环境中优化癌症免疫治疗和精准肿瘤学的转化机会和挑战。
