肿瘤细胞治疗研究
英文原题：Dissecting the immune infiltrate of primary luminal B-like breast carcinomas in relation to age.
Dissecting the immune infiltrate of primary luminal B-like breast carcinomas in relation to age.
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患者被分为三个不重叠的年龄组（35-45 岁＝“年轻组”，n＝12；55-65 岁＝“中年组”，n＝15；≥70 岁＝“老年组”，n＝26）。
衰老对管腔型乳腺癌（Lum-BC）免疫景观的影响尚不明确。理解Lum-BC中免疫编辑的年龄相关动态，有望提高老年患者免疫治疗的疗效。为此，我们在此应用了“抗体新沉积多重迭代标记”（MILAN）技术，这是一种空间分辨的单细胞多重免疫组化方法。我们通过从前瞻性单中心IMAGE（免疫系统与衰老）研究中入组的一组未经治疗患者中采集管腔型乳腺肿瘤的肿瘤中心和浸润前沿，构建了组织芯片。患者被分为三个不重叠的年龄类别（35-45岁＝“年轻”，n = 12；55-65岁＝“中年”，n = 15；≥70岁＝“老年”，n = 26）。此外，根据细胞毒性T淋巴细胞的位置和数量，鉴定出肿瘤免疫类型“荒漠型”（n = 22）、“排斥型”（n = 19）和“炎症型”（n = 12）。对于MILAN技术，我们使用了58种标记物，包括表型和功能标记物，可对T和B淋巴细胞（T&B-lym）进行深入表征。使用Wilcoxon检验和Pearson相关性分析，在年龄组和肿瘤免疫类型之间进行比较。细胞计量分析显示，免疫细胞区室随衰老而下降。与年轻患者相比，中年和老年患者肿瘤中的T&B-lym在数量上较少，无论肿瘤的地理区域如何。同样，荒漠型肿瘤显示出最小的免疫细胞区室，并且未出现在年轻患者组中。免疫检查点分子分析揭示了异质性的地理表达模式，表明年轻患者中PD-L1和OX40阳性T&B淋巴细胞数量高于老年患者。尽管免疫浸润数量下降，但与中年和年轻患者相比，老年患者靠近癌细胞的T辅助细胞中OX40表达水平更高。衰老与Lum-BC免疫景观的重要数量和功能变化相关。© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The impact of aging on the immune landscape of luminal breast cancer (Lum-BC) is poorly characterized. Understanding the age-related dynamics of immune editing in Lum-BC is anticipated to improve the therapeutic benefit of immunotherapy in older patients. To this end, here we applied the 'multiple iterative labeling by antibody neo-deposition' (MILAN) technique, a spatially resolved single-cell multiplex immunohistochemistry method. We created tissue microarrays by sampling both the tumor center and invasive front of luminal breast tumors collected from a cohort of treatment-naïve patients enrolled in the prospective monocentric IMAGE (IMmune system and AGEing) study. Patients were subdivided into three nonoverlapping age categories (35-45 = 'young', n = 12; 55-65 = 'middle', n = 15; ≥70 = 'old', n = 26). Additionally, depending on localization and amount of cytotoxic T lymphocytes, the tumor immune types 'desert' (n = 22), 'excluded' (n = 19), and 'inflamed' (n = 12) were identified. For the MILAN technique we used 58 markers comprising phenotypic and functional markers allowing in-depth characterization of T and B lymphocytes (T&B-lym). These were compared between age groups and tumor immune types using Wilcoxon's test and Pearson's correlation. Cytometric analysis revealed a decline of the immune cell compartment with aging. T&B-lym were numerically less abundant in tumors from middle-aged and old compared to young patients, regardless of the geographical tumor zone. Likewise, desert-type tumors showed the smallest immune-cell compartment and were not represented in the group of young patients. Analysis of immune checkpoint molecules revealed a heterogeneous geographical pattern of expression, indicating higher numbers of PD-L1 and OX40-positive T&B-lym in young compared to old patients. Despite the numerical decline of immune infiltration, old patients retained higher expression levels of OX40 in T helper cells located near cancer cells, compared to middle-aged and young patients. Aging is associated with important numerical and functional changes of the immune landscape in Lum-BC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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