肿瘤细胞治疗研究
英文原题：Targeting of the CD161 Inhibitory Receptor Enhances Bone-Marrow-Resident Memory CD8(+) T-Cell-Mediated Immunity against Multiple Myeloma.
免疫检查点抑制剂（ICIs）已经改变了多种实体瘤的治疗。
免疫检查点抑制剂（ICI）已改变多种实体瘤治疗，但其治疗多发性骨髓瘤（MM）的效果仍不理想，凸显探索传统 ICI 以外替代策略的必要性。本研究发现 CD161 是骨髓（BM）组织驻留记忆 CD8⁺ T 细胞（CD8⁺ TRM）上的新型抑制性受体；这些细胞在 MM 骨髓肿瘤微环境中持续存在并在局部免疫监视中发挥重要作用。CD161 与 MM 细胞上的 CLEC2D 相互作用形成的 CD161-CLEC2D 轴介导免疫抑制和 TRM 功能障碍。阻断 CD161 可增强 TRM 功能，包括组织驻留、增殖和抗肿瘤活性。CD161 阻断还可显著减轻 CAR-T 耗竭，并在体外增强其抗骨髓瘤功能。这些发现确定 CD161-CLEC2D 通路是 MM 免疫治疗的潜在新靶点。
Immune checkpoint inhibitors (ICIs) have transformed the treatment of many solid tumors. Still, their effectiveness in multiple myeloma (MM) remains underwhelming, highlighting the need to explore alternative approaches beyond conventional ICIs. Here, CD161 is identified as a novel inhibitory receptor on bone marrow (BM) tissue resident memory CD8 + T cells (CD8 + TRM), known for their sustained presence and vital role in local immune surveillance in MM BM tumor microenvironments. The CD161-CLEC2D axis, where CD161 interacts with CLEC2D on MM cells, mediates immune suppression and TRM dysfunction. Blocking CD161 enhances TRM function, including tissue residency, proliferation, and antitumor activity. CD161 blockade significantly alleviates chimeric antigen receptor T-cell (CAR-T) exhaustion and enhances their antimyeloma function ex vivo. These findings identified the CD161-CLEC2D pathway as a potential novel target for immunotherapy of MM.
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