PO.PS01.03 · 人群科学
骨髓中性别特异性的浆细胞-免疫结构差异可预测多发性骨髓瘤的总生存期
Sex-specific plasma-immune architectural differences in bone marrow predicts overall survival in multiple myeloma
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摘要 Abstract
中文摘要
背景：多发性骨髓瘤（MM）对男性的影响更大（57%对女性43%），但这些性别差异的生物学基础仍未得到探索。骨髓免疫微环境，尤其是浆细胞-免疫空间组织，在疾病进展和治疗反应中发挥关键作用。新出现的证据表明，性别特异性的免疫学差异促成了癌症生物学和结局的差异，但这些模式在MM中的特征仍描述不足。理解浆细胞-免疫结构特征是否因性别而异以及它们是否具有预后价值，可能为MM中更个性化的风险分层提供依据。
方法：我们从Cancer Moonshot Biobank识别出104张MM全切片骨髓活检。使用预训练的深度学习模型对免疫细胞进行分割，随后进行浆细胞检测。在肿瘤周围和非肿瘤区室中量化浆细胞和其他免疫细胞的形态学（密度和空间）模式，并进行FDR校正的Welch's t检验以比较性别特异性差异。使用单变量Cox比例风险模型评估这些特征的预后关联。
结果：在比较免疫细胞表型时，男性表现出相对于肿瘤密度更高的浆细胞密度（0.158对女性0.105，FDR p=0.029）。空间分析显示男性在肿瘤周围间质中也具有更高的浆细胞-淋巴细胞簇重叠（0.418对女性0.238，FDR p= 0.036）。在生存分析中，浆细胞-淋巴细胞簇的重叠可预测总生存期：HR = 1.730（95% CI：1.074-2.787），p= 0.018，c-index = 0.552。相比之下，淋巴细胞的密度或空间特征在性别之间无显著差异。
结论：尽管淋巴细胞形态无显著差异，浆细胞在密度和空间排列上表现出性别特异性差异。这些性别特异性模式似乎可预测生存，支持了在MM中开展性别分层风险评估和个性化预后策略的必要性。
查看英文原文 English abstract
Background: Multiple myeloma (MM) disproportionately affects men (57% vs. 43% women), yet the biological basis for these sex differences remains unexplored. The bone-marrow immune microenvironment, particularly plasma-immune spatial organisation, plays a critical role in disease progression and therapeutic response. Emerging evidence suggests that sex-specific immunologic differences contribute to disparities in cancer biology and outcomes, yet these patterns remain poorly characterised in MM. Understanding whether plasma-immune architectural features differ by sex and whether they carry prognostic value may inform more personalised risk stratification in MM.
Methods: We identified 104 MM whole-slide bone-marrow biopsies from the Cancer Moonshot Biobank. Using pre-trained deep learning models, immune cells were segmented, followed by plasma cell detection. Morphological (density and spatial) patterns of plasma cells and other immune cells were quantified in peri-tumoral and non-tumoral compartments, and FDR-corrected Welch's t-tests were performed to compare gender specific differences. Prognostic associations of these features were assessed using univariate Cox proportional hazard models.
Results: On comparing the immune cell phenotypes, males exhibited higher plasma density relative to tumor density (0.158 vs female 0.105, FDR p=0.029). Spatial analysis showed that males also had higher plasma-lymphocyte cluster overlap in the peri-tumoral stroma (0.418 vs female 0.238, FDR p= 0.036). In survival analysis, overlap of plasma-lymphocyte cluster was prognostic of overall survival: HR = 1.730 (95% CI: 1.074-2.787), p= 0.018, c-index = 0.552. In contrast, there were no significant differences in density or spatial features of lymphocytes across the genders.
Conclusions: Plasma cell shows gender specific differences in density and spatial arrangement, despite no significant differences in lymphocyte morphology. These sex-specific patterns appear to predict survival, supporting the need for sex-stratified risk assessment and personalised prognostication strategies in MM.
利益披露 Disclosure
D. Raghavan, None..
A. Madabhushi, None..
A. Singh, None..
T. Pathak, None..
G. Corredor, None..
A. Madabhushi, None.