PDF(Pubmed)
Abstract：
The capacity of lymphocytes continuously home to lymphoid structures is remarkable for cancer immunosurveillance and immunotherapy. Lymphocyte homing and recirculation within the tumor microenvironment (TME) are now understood to be adaptive processes that are regulated by specialized cytokines and adhesion molecule signaling cascades. Restricted lymphocyte infiltration and recirculation have emerged as key mechanisms contributing to poor responses in cancer immunotherapies like chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockades (ICBs). Uncovering the kinetics of lymphocytes in tumor infiltration and circulation is crucial for improving immunotherapies. In this review, we discuss the current insights into the adhesive and migrative molecules involved in lymphocyte homing and transmigration. The potential mechanisms within the TME that restrain lymphocyte infiltration are also summarized. Advanced on these, we outline the determinates for tertiary lymphoid structures (TLSs) formation within tumors, placing high expectations on the prognostic values of TLSs as therapeutic targets in malignancies.
摘要：
淋巴细胞连续归巢到淋巴结构的能力对于癌症免疫监视和免疫疗法是显著的。肿瘤微环境（TME）内的淋巴细胞归巢和再循环现在被理解为是由专门的细胞因子和粘附分子信号级联调节的适应性过程。限制性淋巴细胞浸润和再循环已成为导致癌症免疫疗法如嵌合抗原受体(CAR)-T细胞疗法和免疫检查点阻断(ICB)中应答不良的关键机制。揭示淋巴细胞在肿瘤浸润和循环中的动力学对于改善免疫疗法至关重要。在这次审查中,我们讨论了目前对参与淋巴细胞归巢和迁移的粘附和迁移分子的见解。还总结了TME内抑制淋巴细胞浸润的潜在机制。先进的这些，我们概述了肿瘤内三级淋巴结构（TLSs）形成的决定因素，对TLS作为恶性肿瘤治疗靶点的预后价值寄予厚望。
