Background: We have previously shown the remarkable impact of a single infusion of supercharged NK cells (sNK) in preventing and eliminating oral, pancreatic, and uterine cancers implanted in humanized BLT (hu-BLT) mice. Objective: In this report, we extended the studies to melanoma tumors to observe whether there were differences in response to sNK cells. Methods: We investigated the safety and tissue biodistribution profile of sNK cells in hu-BLT mice. This included the effect of sNK cell therapy on the peripheral blood-derived PBMCs, bone marrow, and spleen of hu-BLT mice. Results: Our investigation showed promising outcomes, as sNK cell infusions effectively inhibited melanoma tumor growth in hu-BLT mice. These potent cells not only traversed through the peripheral blood, spleen, and bone marrow but also infiltrated the tumor site, triggering in vivo differentiation of melanoma tumors. Moreover, the infusion of sNK cells increased the percentages of NK cells in the peripheral blood of hu-BLT mice, restoring cytotoxicity and IFN-γ secretion within the peripheral blood, spleen, and bone marrow of melanoma-bearing mice. Conclusions: This therapeutic approach not only reversed tumor progression but also revitalized the functionality of endogenous NK cells, potentially reversing the immunosuppressive effects induced by tumor cells in cancer patients.
背景：我们先前的研究已证实，单次输注超强自然杀伤细胞（sNK）在预防和消除人源化BLT（hu-BLT）小鼠口腔癌、胰腺癌及子宫癌移植瘤方面具有显著效果。目的：本研究将观察范围扩展至黑色素瘤，旨在探究sNK细胞对不同肿瘤类型的疗效差异。方法：我们系统评估了sNK细胞在hu-BLT小鼠体内的安全性与组织分布特征，重点分析sNK细胞疗法对外周血单个核细胞、骨髓及脾脏免疫细胞群的影响。结果：研究显示sNK细胞输注能有效抑制hu-BLT小鼠黑色素瘤生长。这些高活性细胞不仅在外周血、脾脏和骨髓中广泛分布，还能特异性浸润肿瘤部位，引发黑色素瘤体内分化。值得注意的是，sNK细胞输注显著提升了荷瘤小鼠外周血中NK细胞比例，并重建了外周血、脾脏及骨髓中细胞毒性功能与γ干扰素分泌能力。结论：该疗法不仅能够逆转肿瘤进展，还可重塑内源性NK细胞功能，有望逆转肿瘤细胞在癌症患者体内诱导的免疫抑制状态。
肿瘤(癌症)患者之家