为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma.
Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma.
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TIL 浸润水平在 ALPPS 术前阶段维持动态平衡。
TIL(肿瘤浸润淋巴细胞)在肝细胞癌(HCC)生长和进展中的作用受到广泛关注。
通过探究肿瘤微环境中的TIL作用,评估联合肝脏分隔与门静脉结扎分期肝切除术(ALPPS)治疗巨大HCC的可行性。
纳入15例接受ALPPS治疗的巨大HCC患者和46例接受半肝切除术的患者。采用倾向评分匹配,使ALPPS组与半肝切除组患者按1:1匹配。通过免疫荧光染色定量分析两组肿瘤及邻近组织中的TIL,并结合肿瘤学特征进一步分析。同时比较围手术期两组外周血TIL变化趋势。
连续测量肿瘤体积和坏死体积显示,ALPPS一期术后第7天肿瘤坏死体积比例显著高于术前(P=0.024)。ALPPS一期术前,CD8+ T细胞浸润高组的肿瘤坏死体积比例显著高于低浸润组(P=0.048)。
ALPPS术前阶段TIL浸润水平保持动态平衡。与右半肝切除术相比,ALPPS并未导致TIL浸润减少和外周血免疫成分病理变化所提示的严重免疫抑制。结果从免疫学角度提示,ALPPS治疗巨大HCC安全且可行。此外,CD8+ T细胞浸润较高与ALPPS围手术期肿瘤坏死增加相关。
The role of tumor-infiltrating lymphocytes (TILs) in the growth and progression of hepatocellular carcinoma (HCC) has attracted widespread attention. AIM: To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for massive HCC by exploring the role of TIL in the tumor microenvironment.
Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this study. Propensity score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups (1:1). Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological characteristics. In the meantime, trends of TILs in peripheral blood were compared between the two groups during the perioperative period.
Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value ( P = 0.024). In the preoperative period of stage-I ALPPS, the proportion of tumor necrosis volume in the high CD8 + T cell infiltration group was significantly higher than that in the low group ( P = 0.048).
TIL infiltration level maintained a dynamic balance during the preoperative period of ALPPS. Compared with right hemi-hepatectomy, the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral blood. Our results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of immunology. In addition, high CD8 + T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.
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