一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Comparison of Tumor Microenvironments Between Primary Tumors and Brain Metastases in Patients With NSCLC.
Comparison of Tumor Microenvironments Between Primary Tumors and Brain Metastases in Patients With NSCLC.
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我们发现 CD204 阳性细胞在脑转移中更高,这可能对治疗具有更广泛的意义,因为这些巨噬细胞可能具有免疫抑制作用,并使免疫环境反应性降低。此外,放疗后脑转移的癌和间质区域中 CD4+ T 细胞密度更高的发现,支持在 NSCLC 脑转移治疗中将免疫治疗加入放射治疗。
本研究使用多重荧光免疫组化技术,探究了NSCLC患者原发肺肿瘤及相应脑转移灶的免疫特征。
该研究评估了34例因脑转移接受尸检或手术切除的患者,以及因原发性肺癌接受尸检、手术切除或粗针活检的患者。我们通过多重荧光免疫组化分析比较了原发肿瘤和脑转移灶中各种免疫细胞的密度。
与脑转移样本相比,原发性肺癌标本中肿瘤区域和间质区域的CD4阳性(CD4+)T细胞、CD8阳性T细胞和CD4+ Foxp3阳性T细胞的密度在统计学上更高(p < 0.0001)。仅CD204阳性细胞在脑转移的肿瘤区域中在统计学上更高(p = 0.0118)。与脑转移相关的TIL(肿瘤浸润淋巴细胞)与总生存期呈正相关,但原发性肺TIL(肿瘤浸润淋巴细胞)则不然。在接受放疗的脑转移中,癌和间质区域的CD4+和CD4+ Foxp3阳性T细胞密度与未接受放疗者相比在统计学上更高(p = 0.0343,p = 0.0173)。
The study evaluated 34 patients who underwent autopsy or surgical resection for brain metastasis and autopsy, surgical resection, or core biopsy for primary lung cancer. We compared the densities of various immune cells in the primary tumors and the brain metastases by multiplex fluorescence immunohistochemical analysis.
The density of CD4-positive (CD4 + ) T-cells, CD8-positive T-cells, and CD4 + Foxp3-positive T-cells were statistically higher in both tumor and stromal areas in primary lung cancer specimens when compared with brain metastases samples ( p < 0.0001). Only CD204-positive cells were statistically higher in the tumor areas of the brain metastases ( p = 0.0118). Tumor-infiltrating lymphocytes associated with brain metastases positively correlated with overall survival, but primary lung tumor-infiltrating lymphocytes did not. The density of CD4 + and CD4 + Foxp3-positive T-cells in brain metastases with radiation was statistically higher in the carcinoma and stromal areas compared with those without radiation ( p = 0.0343, p = 0.0173).
Our findings that CD204-positive cells were higher in brain metastases may have broader implications for treatment as these macrophages may be immunosuppressive and make the immune environment less reactive. Furthermore, the finding that the density of CD4 + T-cells was higher in cancer and stroma areas of brain metastases after radiotherapy supports the addition of immunotherapy to radiation therapy in the treatment of brain metastases in NSCLC.
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