MediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, Finland.
Turku Doctoral Program of Molecular Medicine, University of Turku, Turku, Finland.
Br J Cancer. 2024 Sep;131(4):627-640. doi: 10.1038/s41416-024-02715-6. Epub 2024 Jun 3.
Tumour-associated macrophages (TAMs) sustain a tumour-supporting and immunosuppressive milieu and therefore aggravate cancer prognosis. To modify TAM behaviour and unlock their anti-tumoural potential, novel TAM-reprogramming immunotherapies are being developed at an accelerating rate. At the same time, scientific discoveries have highlighted more sophisticated TAM phenotypes with complex biological functions and contradictory prognostic associations. To understand the evolving clinical landscape, we reviewed current and past clinically evaluated TAM-reprogramming cancer therapeutics and summarised almost 200 TAM-reprogramming agents investigated in more than 700 clinical trials. Observable overall trends include a high frequency of overlapping strategies against the same therapeutic targets, development of more complex strategies to improve previously ineffective approaches and reliance on combinatory strategies for efficacy. However, strong anti-tumour efficacy is uncommon, which encourages re-directing efforts on identifying biomarkers for eligible patient populations and comparing similar treatments earlier. Future endeavours will benefit from considering the shortcomings of past treatment strategies and accommodating the emerging complexity of TAM biology.
肿瘤相关巨噬细胞（TAMs）维持着肿瘤支持和免疫抑制的微环境，因此加重了癌症的预后。为了改变 TAM 的行为并释放其抗肿瘤潜力，新型的 TAM 重编程免疫疗法正在加速发展。与此同时，科学发现强调了更复杂的 TAM 表型，具有复杂的生物学功能和矛盾的预后相关性。为了了解不断发展的临床前景，我们回顾了当前和过去临床评估的 TAM 重编程癌症治疗方法，并总结了在 700 多项临床试验中研究过的近 200 种 TAM 重编程药物。可观察到的总体趋势包括针对相同治疗靶点的重叠策略频率很高，开发更复杂的策略来改进以前无效的方法，以及依赖组合策略来提高疗效。然而，强烈的抗肿瘤疗效并不常见，这促使人们重新努力寻找合格患者群体的生物标志物，并尽早比较类似的治疗方法。未来的努力将受益于考虑过去治疗策略的缺点，并适应 TAM 生物学的新兴复杂性。
