单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
程序性死亡配体 1 (PD-L1) 表达与基于 CD8⁺ TIL（肿瘤浸润淋巴细胞）的肿瘤免疫微环境分型在妇科癌肉瘤中的预后影响及治疗启示
英文原题：Programmed Death Ligand 1 (PD-L1) Expression and CD8 + Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy.
查看英文原题
Programmed Death Ligand 1 (PD-L1) Expression and CD8 + Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy.
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中文摘要
为研究妇科癌肉瘤中程序性死亡配体 1（PD-L1）表达和 CD8⁺ TIL（肿瘤浸润淋巴细胞）的患病率及预后意义，研究者纳入 81 例病例（子宫 68 例、卵巢 12 例、输卵管 1 例），采用组织芯片（芯径 3 mm）对瘤内 TIL 最高区域进行 PD-L1 和 CD8 免疫染色。肿瘤比例评分（TPS）≥1% 和综合阳性评分（CPS）≥1 定义为 PD-L1 阳性。对每个芯片组织核心中的 CD8⁺ TIL 计数，并计算 CD8⁺ TIL 密度（CD8TILD）。病例按 CD8TILD 分类为 CD8 阴性（<1.4/mm²）、CD8 阳性（≥1.4/mm²）和 CD8 高表达（≥14/mm²），并分入 4 种肿瘤免疫微环境（TIME）组：（1）PD-L1 阳性/CD8 阳性；（2）PD-L1 阴性/CD8 阴性；（3）PD-L1 阳性/CD8 阴性；（4）PD-L1 阴性/CD8 阳性。
按 TPS 和 CPS 判定的 PD-L1 表达率分别为 19.8% 和 39.6%。Kaplan-Meier 曲线及 log-rank 分析显示，CD8⁺ TIL 密度较高与 OS 延长相关（CD8 阳性组 P=0.05，CD8 高表达组 P=0.014）；无论肿瘤分期如何，CD8 高表达均与较长 OS 相关（P=0.045，风险比 0.11，95% 置信区间 0.014–0.951）。33% 的患者属于 TIME 组 1。PD-L1 表达和 TIME 分组与 OS 或无进展生存期无关。
研究发现 CD8⁺ TIL 高密度是 OS 较好的独立指标。33% 病例中，PD-L1 表达伴随 CD8⁺ TIL 增多（PD-L1“获得性免疫逃逸”模式），这些患者可能获益于抗 PD-1/PD-L1 治疗。单独的 PD-L1 表达和 TIME 分组不影响妇科癌肉瘤患者生存。
展开英文摘要原文
To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8 + tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) 1% and combined positive score (CPS) 1 were considered positive for PD-L1. CD8 + TILs were counted in each core, and CD8 + TIL density (CD8TILD) was calculated. Cases were classified as CD8 Neg (<1. 4/mm 2 CD8TILD), CD8 Pos ( 1.
4/mm 2 CD8TILD) and CD8 HIGH ( 14/mm 2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1 Pos /CD8 Pos , (2) PD-L1 Neg /CD8 Neg , (3) PD-L1 Pos /CD8 Neg , and (4) PD-L1 Neg /CD8 Pos . PD-L1 expression by TPS and CPS was detected in 19. 8% and 39. 6% cases, respectively. Kaplan-Meier curves with log-rank analysis showed that higher density of CD8 + TILs were associated with longer overall survival (OS) ( P =0.
05 for CD8 Pos and P =0. 014 for CD8 HIGH ), and CD8 HIGH status was associated with longer OS irrespective of tumor stage ( P =0. 045, hazard ratio: 0. 11, 95% confidence interval: 0. 014-0. 951). Thirty-three percent of patients belonged to TIME group 1. PD-L1 expression and TIME groups were not associated with OS or progression-free survival.
We found that high density of CD8 + TILs is an independent indicator of better OS. In 33% cases PD-L1 expression is associated with increased CD8 + TILs ("acquired immune evasion" pattern of PD-L1 expression), hence they may benefit from anti PD-1/PD-L1 therapy. PD-L1 expression alone and TIME groups do not affect survival in gynecologic carcinosarcoma.
论文信息
- 作者
- Ordner J、Gutierrez Amezcua JM、Marcus A、Shukla PS
- 第一作者单位
- Department of Pathology, NYU Langone Health, New York, New York.United States
- 期刊
- International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists2023 Jul 1
- 原文标识
- PubMed 35639400 · DOI 10.1097/PGP.0000000000000890