肿瘤细胞治疗研究
英文原题：Chemotherapy driven alterations in NK cell receptors and ligands in high grade serous ovarian cancer.
我们的发现凸显了化疗对NK细胞受体、配体和细胞因子的广泛免疫调节作用，这可能为HGSOC的联合治疗提供见解。
目前正在探索联合治疗方案以提高免疫治疗疗效，但在高级别浆液性卵巢癌（HGSOC）中，化疗对NK细胞受体及其配体的免疫调节作用尚未被探索。因此，了解化疗诱导的免疫调节在HGSOC中至关重要。
对33例接受初次肿瘤细胞减灭术（PDS）的未化疗患者、57例接受间歇性肿瘤细胞减灭术（IDS）的化疗后患者进行了临床标本的免疫分析，其中17例IDS组患者在化疗周期中进行了随访。免疫分析采用流式细胞术、Procartaplex免疫测定和ELISA进行。采集了50例年龄和性别匹配的健康参与者的血液样本用于比较。
对随访患者的初步研究揭示了化疗介导的对NK细胞亚群的免疫调节。这一点在化疗治疗的手术队列中得到了进一步验证。在未接受化疗的手术队列中，NK细胞上的自然细胞毒性受体（NCRs）表达下调。在化疗治疗的手术队列中，由于可溶性配体减少，NCR组受体恢复至与健康对照相当的水平。与未接受化疗的手术队列相比，化疗治疗的手术队列中EpCAM+细胞上的表面MICA表达也增加（p = 0.0466），而两个手术队列中NKG2D+免疫细胞均较健康对照减少。此外，化疗治疗的手术队列中促炎细胞因子IL-2（p = 0.0001）和TNF-α（p = 0.0442）降低，而化疗治疗组中穿孔素和颗粒酶的双重细胞内水平升高，这可能增强细胞溶解潜力。HLA-E、MIC-B和LLT-1配体的高表面表达与改善的无进展生存期相关。
INTRODUCTION: Combination approaches are being explored to improve immunotherapy efficacy, yet the immunomodulatory effects of chemotherapy on NK cell receptors and their ligands remain unexplored in high-grade serous ovarian cancer (HGSOC). Therefore, understanding chemotherapy-induced immune modulation is essential in HGSOC. METHODS: Immune profiling was conducted on clinical specimens from 33 chemo-naïve patients undergoing primary debulking surgery (PDS), 57 chemotherapy-treated patients undergoing interval debulking surgery (IDS), and 17 patients in the IDS group were followed during chemotherapy cycles. Immune profiling was carried out using flow cytometry, Procartaplex immunoassay, and ELISA. Blood samples were collected from 50 age- and gender-matched healthy participants for comparison. RESULTS: Primary investigation on follow-up patients reveals chemotherapy-mediated immune modulation on NK cell subsets. This was further validated in the chemo-treated surgical cohort. The Natural Cytotoxicity Receptors (NCRs) were downregulated on NK cells in chemo-naïve surgical cohorts. The NCR group of receptors was normalized to a level comparable to that in healthy controls in the chemotherapy-treated surgical cohort, due to reduced soluble ligands. Surface MICA expression was also increased (p = 0.0466) on EpCAM+ cells in the chemo-treated surgical cohort compared to the chemo-naïve surgical cohort, while NKG2D+ immune cells were reduced in both surgical cohorts compared to healthy controls. Moreover, proinflammatory cytokines IL-2 (p = 0.0001) and TNF-α (p = 0.0442) were reduced in the chemotherapy-treated surgical cohort, while intracellular levels of dual perforin and granzyme were elevated in the chemo-treated group, which may enhance cytolytic potential. High surface expressions of HLA-E, MIC-B, and LLT-1 ligands were associated with improved progression-free survival. CONCLUSIONS: Our findings highlight the broad immunomodulatory effects of chemotherapy on NK cell receptors, ligands, and cytokines, which may offer insights for combination therapies in HGSOC.
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