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
HHLA2 免疫检查点是肝细胞癌的一种新型预后预测因子
英文原题：HHLA2 Immune Checkpoint Is a Novel Prognostic Predictor in Hepatocellular Carcinoma.
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HHLA2 Immune Checkpoint Is a Novel Prognostic Predictor in Hepatocellular Carcinoma.
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研究概要
HHLA2 在 HCC 中频繁表达。HHLA2 阳性与较高的 CD8+细胞密度和良好的预后相关。HHLA2 可能被视为 HCC 中潜在的治疗性免疫靶点。
研究思路结论见上方概要
目的
靶向PD-1/PD-L1的免疫治疗在肝细胞癌（HCC）患者中缓解率低，总生存期获益有限。我们描述了B7家族免疫检查点蛋白HHLA2、PD-L1和B7-H4在HCC中的表达模式及临床意义。
方法
对103例手术切除的HCC标本的组织芯片切片进行了HHLA2、PD-L1、B7-H4、CD3和CD8的免疫组化染色。
结果
检测到HHLA2阳性63例（61.2%），其中50例低表达，13例高表达。检测到PD-L1阳性（联合阳性评分[CPS]≥1）27例（26.2%），其中大多数为低表达（CPS<10）（n=25），仅2例为高表达（CPS≥10）。观察到PD-L1和HHLA2共表达17例（16.5%）。仅1例（1.0%）检测到B7-H4表达。HHLA2阳性病例的生存期显著优于HHLA2阴性病例（P=.042）。HHLA2阳性与更高的CD8+瘤内淋巴细胞密度相关（P=.015）。HHLA2表达且CD8+细胞密度高的亚组表现出最有利的预后（P=.036）。
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OBJECTIVES
Immunotherapy targeting PD-1/PD-L1 had low response rates and limited overall survival benefits in patients with hepatocellular carcinoma (HCC). We characterized the expression pattern and clinical significance of B7 family immune checkpoint proteins HHLA2, PD-L1, and B7-H4 in HCC.
METHODS
Immunohistochemistry for HHLA2, PD-L1, B7-H4, CD3, and CD8 was performed on tissue microarray slides from 103 surgically resected HCC specimens.
RESULTS
Positive HHLA2 was detected in 63 (61.2%) cases, with 50 cases showing low expression and 13 cases showing high expression. Positive PD-L1 (combined positive score [CPS] ≥1) was detected in 27 (26.2%) cases, with the majority showing low expression (CPS <10) (n = 25) and only 2 cases showing high expression (CPS ≥10). The coexpression of PD-L1 and HHLA2 was observed in 17 (16.5%) cases. B7-H4 expression was detected in only one (1.0%) case. HHLA2-positive cases had significantly better survival than HHLA2-negative cases (P = .042). Positive HHLA2 correlated with higher density of CD8+ intratumoral lymphocytes (P = .015). The subgroup with both HHLA2 expression and high CD8+ cell density exhibited the most favorable prognosis (P = .036).
CONCLUSIONS
HHLA2 is frequently expressed in HCC. Positive HHLA2 correlates with higher CD8+ cell density and favorable prognosis. HHLA2 may be considered a potential therapeutic immune target in HCC.
论文信息
- 作者
- Liao X、Zhang D
- 单位
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.United States
- 期刊
- American journal of clinical pathology2022 Jul 1
- 原文标识
- PubMed 35084443 · DOI 10.1093/ajcp/aqab221