■术中放射治疗(IORT)在保乳手术(BCS)期间向乳腺肿瘤床提供单次加速辐射剂量。同时手术和放疗的协同生物学效应仍不清楚。本研究探讨了IORT在肿瘤微环境中诱导的细胞和分子变化及其对免疫应答调节的影响。
■激素受体(HR)阳性/HER2阴性的患者,导管原位癌(DCIS),纳入或早期浸润性乳腺癌行BCS伴边缘再切除。比较了IORT患者(n=11)与再次切除组织的组织病理学评估和RNA测序非IORT(n=11)。
■在IORT标本中只发现了异型鳞状上皮化生(63.6%,p=0.004),模仿DCIS。然后我们鉴定了IORT和非IORT样品之间的1,662个差异表达基因(875个上调和787个下调)。基因本体论分析表明,IORT与几种免疫应答途径的富集有关,如炎症反应,粒细胞激活,和T细胞活化(p<0.001)。当只考虑来自两个队列的正常组织时,IORT与内在凋亡信号有关,对伽马辐射的响应,和程序性细胞死亡的正向调节(p<0.001)。使用xCell算法,我们推断γδT细胞的丰度更高,树突状细胞,和IORT样品中的单核细胞。
■IORT诱导组织学变化,包括鳞状上皮化生与异型,并引发与免疫反应和内在凋亡途径相关的分子改变。暴露于IORT的乳腺组织中免疫相关成分的丰度增加表明了向活性免疫原性的潜在转变。特别是免疫沙漠肿瘤,如HR阳性/HER2阴性乳腺癌。
UNASSIGNED: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation.
UNASSIGNED: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11).
UNASSIGNED: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples.
UNASSIGNED: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.