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Abstract：
UNASSIGNED: The efficacy of immunotherapy for brain metastases from small cell lung cancer (SCLC) is relatively low, and the tumor microenvironment of SCLC brain metastases is still unknown. Therefore, we investigated the distribution of tumor-infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) in patients with brain metastases from SCLC to explore the tumor microenvironment of SCLC brain metastases.
UNASSIGNED: A retrospective analysis was performed on 12 surgical specimens of brain metastases from patients with SCLC treated in the Department of Neurosurgery of The First Affiliated Hospital of Anhui Medical University from June 2017 to June 2022. The inclusion criteria for this study were the following: (I) a pathologically confirmed diagnosis of SCLC brain metastases; (II) surgical resection of brain metastases; (III) age >18 years; (IV) and complete clinical data. Patient-related data were retrieved from the inpatient medical record system, telephone follow-up of patients date of death, and overall survival (OS). The immunofluorescence-based tissue microenvironment analysis panel (MAP) was utilized for the detection of TILs, including CD3, CD8, programmed cell death 1 (PD-1), and PD-L1, in formalin-fixed and paraffin-embedded archival specimens of brain metastases. The expression levels of PD-L1 in tumor cells were detected by immunohistochemistry. The correlation between the OS and the above-mentioned markers was analyzed in the 12 patients.
UNASSIGNED: Twelve patients were included in the study. The patients\' ages ranged from 51-78 years with a median of 68 years, with 1 female and 11 males. Among 12 patients with SCLC brain metastases: positive rates of CD3+ TILs in the tumor parenchyma vs. tumor stroma were 0.60%±0.94% vs. 1.76%±2.72% (P=0.01), respectively; positive rates of CD8+ TILs in the tumor parenchyma vs. tumor stroma were 0.80%±0.78% vs. 2.46%±3.72% (P=0.02), respectively. There was no co-expression of CD8+ and PD-1+ TILs in the tumor parenchyma of 11 cases, and the infiltration density of coexpressed CD3+ and PD-1+ TILs was more than 10/mm2 in only 1 case. There was no coexpression of CD3+ and PD-1+ TIL in the stroma of 10 cases, and the infiltration density of CD8+ and PD-1+ TILs was more than 10/mm2 in 2 cases. Immunohistochemistry was used to detect the expression of PD-L1 in 12 cases of SCLC metastatic lesions, and 3 cases (25%) were positive. Survival analysis showed that patients with positive intraepithelial CD3+ TILs had significantly longer OS [hazard ratio 3.383, 95% confidence interval (CI): 0.959-11.940; P=0.04].
UNASSIGNED: Our study further demonstrated the immune microenvironment of SCLC brain metastases. The distribution of TILs in SCLC brain metastases is low and mainly distributed in the stroma, with the expression of PD-L1 in these tumor tissues being low. Further exploration of the immune microenvironment of SCLC brain metastases is of great significance for potential treatment.
UNASSIGNED: A retrospective analysis was performed on 12 surgical specimens of brain metastases from patients with SCLC treated in the Department of Neurosurgery of The First Affiliated Hospital of Anhui Medical University from June 2017 to June 2022. The inclusion criteria for this study were the following: (I) a pathologically confirmed diagnosis of SCLC brain metastases; (II) surgical resection of brain metastases; (III) age >18 years; (IV) and complete clinical data. Patient-related data were retrieved from the inpatient medical record system, telephone follow-up of patients date of death, and overall survival (OS). The immunofluorescence-based tissue microenvironment analysis panel (MAP) was utilized for the detection of TILs, including CD3, CD8, programmed cell death 1 (PD-1), and PD-L1, in formalin-fixed and paraffin-embedded archival specimens of brain metastases. The expression levels of PD-L1 in tumor cells were detected by immunohistochemistry. The correlation between the OS and the above-mentioned markers was analyzed in the 12 patients.
UNASSIGNED: Twelve patients were included in the study. The patients\' ages ranged from 51-78 years with a median of 68 years, with 1 female and 11 males. Among 12 patients with SCLC brain metastases: positive rates of CD3+ TILs in the tumor parenchyma vs. tumor stroma were 0.60%±0.94% vs. 1.76%±2.72% (P=0.01), respectively; positive rates of CD8+ TILs in the tumor parenchyma vs. tumor stroma were 0.80%±0.78% vs. 2.46%±3.72% (P=0.02), respectively. There was no co-expression of CD8+ and PD-1+ TILs in the tumor parenchyma of 11 cases, and the infiltration density of coexpressed CD3+ and PD-1+ TILs was more than 10/mm2 in only 1 case. There was no coexpression of CD3+ and PD-1+ TIL in the stroma of 10 cases, and the infiltration density of CD8+ and PD-1+ TILs was more than 10/mm2 in 2 cases. Immunohistochemistry was used to detect the expression of PD-L1 in 12 cases of SCLC metastatic lesions, and 3 cases (25%) were positive. Survival analysis showed that patients with positive intraepithelial CD3+ TILs had significantly longer OS [hazard ratio 3.383, 95% confidence interval (CI): 0.959-11.940; P=0.04].
UNASSIGNED: Our study further demonstrated the immune microenvironment of SCLC brain metastases. The distribution of TILs in SCLC brain metastases is low and mainly distributed in the stroma, with the expression of PD-L1 in these tumor tissues being low. Further exploration of the immune microenvironment of SCLC brain metastases is of great significance for potential treatment.
摘要：
■免疫疗法治疗小细胞肺癌（SCLC）脑转移的疗效相对较低，SCLC脑转移瘤的肿瘤微环境尚不清楚。因此,我们研究了SCLC脑转移患者肿瘤浸润淋巴细胞(TIL)的分布和程序性细胞死亡配体1(PD-L1)的表达,以探讨SCLC脑转移的肿瘤微环境.
■回顾性分析2017年6月至2022年6月安徽医科大学第一附属医院神经外科收治的12例SCLC患者脑转移标本。本研究的纳入标准如下:(I)经病理证实诊断为SCLC脑转移瘤;(II)手术切除脑转移瘤;(III)年龄>18岁;(IV)临床资料完整。从住院病历系统检索患者相关数据，患者死亡日期的电话随访，总生存率（OS）。基于免疫荧光的组织微环境分析面板（MAP）用于TIL的检测，包括CD3，CD8，程序性细胞死亡1（PD-1），和PD-L1，在福尔马林固定和石蜡包埋的脑转移档案标本中。免疫组化法检测肿瘤细胞中PD-L1的表达水平。分析了12例患者的OS与上述标志物之间的相关性。
■12名患者被纳入研究。患者年龄为51-78岁，中位数为68岁，有1名女性和11名男性。在12例SCLC脑转移患者中：肿瘤实质中CD3TIL的阳性率与肿瘤间质为0.60%±0.94%vs.1.76%±2.72%(P=0.01),分别；肿瘤实质中CD8+TIL阳性率与肿瘤间质为0.80%±0.78%vs.2.46%±3.72%(P=0.02),分别。11例肿瘤实质中CD8+和PD-1+TILs均无共表达,仅1例，共表达CD3+和PD-1+TIL的浸润密度大于10/mm2。10例间质中无CD3+和PD-1+TIL共表达,2例CD8+和PD-1+TILs浸润密度均大于10/mm2。采用免疫组织化学方法检测12例SCLC转移灶中PD-L1的表达,阳性3例(25%)。生存分析显示，上皮内CD3+TILs阳性患者的OS显著延长[风险比3.383，95%置信区间（CI）：0.959-11.940；P=0.04]。
■我们的研究进一步证明了SCLC脑转移的免疫微环境。TILs在SCLC脑转移中的分布较低，主要分布在间质中，这些肿瘤组织中PD-L1的表达较低。进一步探索SCLC脑转移的免疫微环境对潜在治疗具有重要意义。
■回顾性分析2017年6月至2022年6月安徽医科大学第一附属医院神经外科收治的12例SCLC患者脑转移标本。本研究的纳入标准如下:(I)经病理证实诊断为SCLC脑转移瘤;(II)手术切除脑转移瘤;(III)年龄>18岁;(IV)临床资料完整。从住院病历系统检索患者相关数据，患者死亡日期的电话随访，总生存率（OS）。基于免疫荧光的组织微环境分析面板（MAP）用于TIL的检测，包括CD3，CD8，程序性细胞死亡1（PD-1），和PD-L1，在福尔马林固定和石蜡包埋的脑转移档案标本中。免疫组化法检测肿瘤细胞中PD-L1的表达水平。分析了12例患者的OS与上述标志物之间的相关性。
■12名患者被纳入研究。患者年龄为51-78岁，中位数为68岁，有1名女性和11名男性。在12例SCLC脑转移患者中：肿瘤实质中CD3TIL的阳性率与肿瘤间质为0.60%±0.94%vs.1.76%±2.72%(P=0.01),分别；肿瘤实质中CD8+TIL阳性率与肿瘤间质为0.80%±0.78%vs.2.46%±3.72%(P=0.02),分别。11例肿瘤实质中CD8+和PD-1+TILs均无共表达,仅1例，共表达CD3+和PD-1+TIL的浸润密度大于10/mm2。10例间质中无CD3+和PD-1+TIL共表达,2例CD8+和PD-1+TILs浸润密度均大于10/mm2。采用免疫组织化学方法检测12例SCLC转移灶中PD-L1的表达,阳性3例(25%)。生存分析显示，上皮内CD3+TILs阳性患者的OS显著延长[风险比3.383，95%置信区间（CI）：0.959-11.940；P=0.04]。
■我们的研究进一步证明了SCLC脑转移的免疫微环境。TILs在SCLC脑转移中的分布较低，主要分布在间质中，这些肿瘤组织中PD-L1的表达较低。进一步探索SCLC脑转移的免疫微环境对潜在治疗具有重要意义。
