Abstract：
Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.
摘要：
三阴性乳腺癌（TNBC）的特征是几种生物标志物的表达丧失。这限制了该疾病的治疗策略。近年来,免疫疗法在各种肿瘤的治疗中显示出有希望的结果。新的证据表明TNBC是一种免疫激活的癌症，表明免疫疗法可能是TNBC的可行治疗选择。细胞因子诱导的杀伤（CIK）细胞疗法被认为是一种潜在的癌症治疗方法。然而,它在临床上仍未被批准为标准治疗。我们先前的研究表明，粘着斑激酶（FAK）在调节TNBC细胞对CIK细胞的敏感性中起重要作用。在这项研究中,我们进一步验证了FAK在体内调节免疫应答中的作用。我们的体外研究表明，在TNBC细胞中敲低FAK或用FAK抑制剂处理，然后与CIK细胞共培养，比仅CIK细胞处理诱导更多的细胞死亡。RNA-seq分析表明，FAK的抑制可能会影响TNBC细胞中几种免疫相关基因的表达，从而影响TNBC细胞肿瘤微环境中的免疫反应。FAK抑制剂和CIK细胞的组合比在体内单独治疗FAK抑制剂或CIK细胞显着抑制肿瘤生长。我们的发现为CIK细胞疗法在TNBC治疗中的细胞毒性作用提供了新的见解，并表明CIK细胞疗法与FAK抑制剂的组合可能是TNBC患者的替代治疗策略。
