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.
尽管癌症治疗已取得显著进展，免疫逃逸仍是影响有效治疗结果的主要障碍。在航天飞行环境中，宇航员暴露于独特的环境压力因素——尤其是微重力和辐射——这些因素深刻影响细胞与免疫稳态。新近证据表明，微重力会改变关键细胞过程，包括增殖、凋亡、黏附以及NF-κB和ERK1/2等致癌信号通路。同时，微重力（µg）会破坏免疫调节，可能促进肿瘤进展和治疗抵抗。尤其值得关注的是，在µg条件下人类内源性逆转录病毒（HERVs），特别是HERV-K和HERV-W的上调，可能加剧炎症反应和免疫系统失调。虽然部分研究表明µg可能抑制肿瘤生长，但其他研究揭示了其增强免疫逃逸和降低抗肿瘤免疫的作用。重要的是，µg研究的见解不仅超越空间医学范畴，更为地面肿瘤学提供了转化机遇，包括开发用于药物筛选的生理相关3D肿瘤模型、鉴定机械敏感通路（FAK/RhoA、YAP/TAZ）作为治疗靶点，以及涉及表观遗传调控和检查点抑制的新型免疫治疗策略。本综述批判性地探讨了µg在调节癌症进展和免疫功能中的双重作用，系统整合了关于µg如何塑造免疫应答、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发现。最后，我们重点阐述了在航天和地面环境中优化癌症免疫治疗与精准肿瘤学的转化机遇与挑战。
肿瘤(癌症)患者之家