Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden.
Front Immunol. 2021 Mar 10;12:640578. doi: 10.3389/fimmu.2021.640578. eCollection 2021.
The growing insights in the complex interactions between metastatic cancer-cells and platelets have revealed that platelet tumor cell interactions in the blood stream are an important factor supporting tumor metastasis. An increased coagulability of platelets facilitates the vascular evasion and establishment of solid tumor metastasis. Furthermore, platelets can support an immunosuppressive tumor microenvironment or shield tumor cells directly from engagement of cytotoxic lymphocytes as e.g., natural killer (NK) cells. Platelets are both in the tumor microenvironment and systemically the quantitatively most important source of TGF-β, which is a key cytokine for immunosuppression in the tumor microenvironment. If similar platelet-tumor interactions are of physiological relevance in hematological malignancies remains less well-studied. This might be important, as T- and NK cell mediated graft vs. leukemia effects (GvL) are well-documented and malignant hematological cells have a high exposure to platelets compared to solid tumors. As NK cell-based immunotherapies gain increasing attention as a therapeutic option for patients suffering from hematological and other malignancies, we review the known interactions between platelets and NK cells in the solid tumor setting and discuss how these could also apply to hematological cancers. We furthermore explore the possible implications for NK cell therapy in patients with solid tumors and patients who depend on frequent platelet transfusions. As platelets have a protective and supportive effect on cancer cells, the impact of platelet transfusion on immunotherapy and the combination of immunotherapy with platelet inhibitors needs to be evaluated.
转移性癌细胞与血小板之间复杂相互作用的研究不断深入，揭示了血液中血小板与肿瘤细胞的相互作用是支持肿瘤转移的一个重要因素。血小板的高凝状态有利于肿瘤细胞逃避血管并形成实体瘤转移。此外，血小板可以支持免疫抑制性肿瘤微环境，或者直接保护肿瘤细胞免受细胞毒性淋巴细胞（如自然杀伤 (NK) 细胞）的攻击。血小板既是肿瘤微环境中的重要成分，也是系统性中 TGF-β 的最重要来源，TGF-β 是肿瘤微环境中免疫抑制的关键细胞因子。如果类似的血小板-肿瘤相互作用在血液恶性肿瘤中具有生理相关性，则研究较少。这可能很重要，因为 T 细胞和 NK 细胞介导的移植物抗白血病效应（GvL）已有充分的文献记载，并且与实体瘤相比，恶性血液细胞与血小板的接触更为频繁。鉴于 NK 细胞为基础的免疫疗法作为治疗血液系统恶性肿瘤和其他恶性肿瘤患者的一种治疗选择受到越来越多的关注，我们回顾了已知的 NK 细胞在实体瘤中的作用，并讨论了这些作用如何也适用于血液系统癌症。我们还探讨了 NK 细胞治疗对实体瘤患者和经常需要血小板输注的患者的可能影响。由于血小板对癌细胞具有保护和支持作用，因此需要评估血小板输注对免疫疗法的影响以及免疫疗法与血小板抑制剂联合应用的效果。
