Tumour-associated macrophages as a potential target to improve natural killer cell-based immunotherapies.
Tumour-associated macrophages as a potential target to improve natural killer cell-based immunotherapies.
复制标题
DOI：
10.1042/ebc20230002
复制
发表时间：
2023-09-28
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
自然杀伤（NK）细胞的连续转移已被提出作为一种新的免疫治疗恶性肿瘤抵抗目前的治疗方式。几项临床研究表明，NK细胞输注耐受性良好，无严重副作用，并在血液系统恶性肿瘤中显示出有希望的结果。然而，恶性实体瘤患者对这种疗法没有显着反应。这种令人失望的结果主要是由于输注的NK细胞的低效递送及其在肿瘤微环境（TME）中的功能受损。肿瘤相关巨噬细胞（TAM）是大多数实体瘤的TME中最丰富的基质细胞，并且高TAM密度与癌症患者的不良预后相关。虽然我们对TAM和NK细胞之间相互作用的了解有限，但许多研究表明TAM抑制NK细胞对癌细胞的细胞毒性。因此，阻断TAM功能可以是改善基于NK细胞的免疫疗法的有吸引力的策略。另一方面，据报道巨噬细胞在某些情况下激活NK细胞。本文介绍了我们目前对巨噬细胞调节NK细胞功能的机制的认识，并讨论了可能的治疗方法来阻断巨噬细胞介导的NK细胞抑制。
Adoptive transfer of natural killer (NK) cells has been proposed as a novel immunotherapy for malignant tumours resistant to current therapeutic modalities. Several clinical studies have demonstrated that the NK cell-infusion is well tolerated without severe side effects and shows promising results in haematological malignancies. However, patients with malignant solid tumours do not show significant responses to this therapy. Such disappointing results largely arise from the inefficient delivery of infused NK cells and the impairment of their functions in the tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are the most abundant stromal cells in the TME of most solid tumours, and a high TAM density correlates with poor prognosis of cancer patients. Although our knowledge of the interactions between TAMs and NK cells is limited, many studies have indicated that TAMs suppress NK cell cytotoxicity against cancer cells. Therefore, blockade of TAM functions can be an attractive strategy to improve NK cell-based immunotherapies. On the other hand, macrophages are reported to activate NK cells under certain circumstances. This essay presents our current knowledge about mechanisms by which macrophages regulate NK cell functions and discusses possible therapeutic approaches to block macrophage-mediated NK cell suppression.