Cho Min Soon, Lee Hani, Gonzalez-Delgado Ricardo, Li Dan, Sasano Tomoyuki, Carlos-Alcalde Wendolyn, Ma Qing, Liu Jinsong, Sood Anil K, Afshar-Kharghan Vahid
Section of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2022 May 19;14(10):2498. doi: 10.3390/cancers14102498.
The interactions between platelets and cancer cells activate platelets and enhance tumor growth. Platelets increase proliferation and epithelial-mesenchymal transition in cancer cells, inhibit anoikis, enhance the extravasation of cancer cells, and protect circulating tumor cells against natural killer cells. Here, we have identified another mechanism by which platelets dampen the immune attack on cancer cells. We found that platelets can blunt the antitumor immune response by increasing the expression of inhibitory immune checkpoint (PD-L1) on ovarian cancer cells in vitro and in vivo. Platelets increased PD-L1 in cancer cells via contact-dependent (through NF-κB signaling) and contact-independent (through TFGβR1/Smad signaling) pathways. Inhibition of NF-κB or TGFβR1 signaling in ovarian cancer cells abrogated platelet-induced PD-L1 expression. Reducing platelet counts or inhibiting platelet functions reduced the expression of PD-L1 in ovarian cancer. On the other hand, an increase in platelet counts increased the expression of PD-L1 in tumor-bearing mice.
血小板与癌细胞之间的相互作用会激活血小板并促进肿瘤生长。血小板可增加癌细胞的增殖和上皮-间质转化，抑制失巢凋亡，增强癌细胞的外渗，并保护循环肿瘤细胞免受自然杀伤细胞的攻击。在此，我们发现了血小板抑制对癌细胞免疫攻击的另一种机制。我们发现，血小板可通过在体外和体内增加卵巢癌细胞上抑制性免疫检查点（PD-L1）的表达来减弱抗肿瘤免疫反应。血小板通过接触依赖性（通过NF-κB信号传导）和非接触依赖性（通过TFGβR1/Smad信号传导）途径增加癌细胞中的PD-L1。抑制卵巢癌细胞中的NF-κB或TGFβR1信号传导可消除血小板诱导的PD-L1表达。降低血小板计数或抑制血小板功能可降低卵巢癌中PD-L1的表达。另一方面，增加血小板计数可增加荷瘤小鼠中PD-L1的表达。
