免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Functional cytokine-based classification of tumor-infiltrating lymphocytes in melanoma.
Functional cytokine-based classification of tumor-infiltrating lymphocytes in melanoma.
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TIL(肿瘤浸润淋巴细胞)是黑色素瘤的重要预后和预测生物标志物。然而,将 TIL 组织学分为密集型、非密集型或缺如仍带有主观性,且容易产生观察者间差异。肿瘤免疫微环境(TIME)受肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)等细胞因子调节,在肿瘤进展和治疗应答中发挥核心作用。
本研究探讨细胞因子免疫评分能否作为 TIL 组织学评估的功能性补充。研究分析了 205 例早期结节型皮肤黑色素瘤,患者均为未经治疗的南非黑人;其中 TIL 密集型 65 例、非密集型 60 例、缺如 80 例。研究采用改良 Allred 法通过免疫组化定量 TNF-α 和 IFN-γ 表达,并与 TIL 分类进行关联分析。由 3 名有经验的病理学家进行细胞因子免疫评分,差异通过共识解决。两种细胞因子均与 TIL 模式显著相关(p<0.001;Cramér V 为 0.31–0.41),表达从 TIL 缺如到非密集型再到密集型逐步升高。Logistic 回归显示,与 TIL 缺如病例相比,非密集型病例细胞因子高表达的优势高 3–4 倍,密集型病例高 6–8 倍。诊断指标显示敏感度和特异度中等,但阴性预测值较强。不一致病例揭示出单靠形态学无法反映的免疫活性。这些结果支持将细胞因子免疫评分作为补充工具,以改进对黑色素瘤 TIME 功能状态的评估。
Tumor-infiltrating lymphocytes (TILs) are important prognostic and predictive biomarkers of melanoma.
However, the histological classification of TILs into brisk, non-brisk, or absent categories remains subjective and prone to inter-observer variability. The tumor immune microenvironment (TIME), regulated by cytokines such as tumor necrosis factor-alpha (TNF- ) and interferon-gamma (IFN- ), plays a central role in tumor progression and therapeutic response.
This study investigated whether cytokine immune scoring could serve as a functional adjunct to histological TIL evaluation. A total of 205 early-stage nodular cutaneous melanoma cases from treatment na ve black South African patients were analyzed (65 brisk, 60 non-brisk, and 80 absent). TNF- and IFN- expression were quantified by immunohistochemistry using a modified Allred method and correlated with TIL categories. Three experienced pathologists took part in cytokine immune scoring and any discrepancies were addressed by consensus.
Both cytokines were significantly associated with TIL patterns ( p < 0. 001, Cram r's V 0. 31-0. 41), with expression increasing from absent to non-brisk to brisk TILs. Logistic regression revealed 3-4-fold higher odds of high cytokine expression in non-brisk and 6-8-fold higher odds in brisk versus absent cases. The diagnostic metrics indicated moderate sensitivity and specificity but strong negative predictive values. Discordant cases revealed immune activity that was not reflected by morphology alone.
These findings support cytokine immune scoring as a complementary tool for refining the functional assessment of the TIME in melanoma.
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