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跨癌种分析揭示治愈性放疗期间独特的免疫调节模式

英文原题:Cross-Cancer Analysis Reveals a Distinct Pattern of Immune Modulation During Curative Radiation Therapy.

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Cross-Cancer Analysis Reveals a Distinct Pattern of Immune Modulation During Curative Radiation Therapy.

PubMed 2025/09/19(内容时间) Int J Radiat Oncol Biol Phys Q1 · IF 7.4(JCR 2025)

研究概要

我们在所有接受RT治疗的肿瘤类型中均发现了一种独特的免疫变化模式,表现为促肿瘤髓系细胞群体增加、B细胞和NK 细胞减少,以及在发生远处转移的患者中CD4效应T细胞显著下降。

研究思路结论见上方概要

放射治疗(RT)是根治性癌症治疗的基石,但其免疫效应尚未完全明确。本研究探讨了接受RT的实体瘤患者全身免疫谱的变化。

接受根治性RT(>45 Gy,1.8-3 Gy/次)治疗的局限性头颈癌、非小细胞肺癌、直肠癌或肢体软组织肉瘤患者被纳入研究。使用多重Luminex细胞因子检测和高维质谱流式细胞术(飞行时间流式细胞术)分析基线和RT后(45 Gy后)血液样本。免疫改变与患者结局相关。

37例接受根治性RT的头颈部癌(n = 8)、非小细胞肺癌(n = 8)、直肠癌(n = 7)或软组织肉瘤(n = 14)患者被纳入研究。约50%的患者接受了同步化疗。在中位随访21个月时,出现了3例局部复发和12例远处复发。细胞因子分析显示C-X-C基序趋化因子配体12(P = .044)和单核细胞趋化蛋白-1(P < .001)升高,二者在单核细胞运输和动员中均具有重要作用。与细胞因子变化一致,飞行时间流式细胞术显示单核细胞增多(P < .001),NK 细胞和B细胞减少(P < .001)。发生远处转移的患者循环CD4效应T细胞减少(P = .049),但在无复发患者中保持不变。这些效应与肿瘤类型和化疗无关,表明RT后存在保守的免疫变化。

展开英文摘要原文

PURPOSE: Radiation therapy (RT) is a cornerstone of curative cancer treatment, yet its immune effects are not fully understood. This study examined systemic immune profile changes in patients undergoing RT for solid tumors. METHODS AND MATERIALS: Patients with localized head and neck cancer, non-small cell lung cancer, rectal cancer, or extremity soft tissue sarcoma treated with curative RT (>45 Gy, 1.8-3 Gy/fraction) were enrolled. Baseline and post-RT (after 45 Gy) blood samples were analyzed using multiplex Luminex cytokine assays and high-dimensional mass cytometry (cytometry by time-of-flight). Immune alterations were correlated with patient outcomes. RESULTS: Thirty-seven patients treated with curative RT for head and neck cancer (n = 8), non-small cell lung cancer (n = 8), rectal cancer (n = 7) or soft tissue sarcoma (n = 14) were enrolled. Approximately 50% of patients received concurrent chemotherapy. At a median follow-up of 21 months, there were 3 local and 12 distant recurrences. Cytokine analysis showed increased C-X-C motif chemokine ligand 12 (P = .044) and monocyte chemoattractant protein-1 (P < .001), both important in monocyte trafficking and mobilization. Consistent with the cytokine changes, cytometry by time-of-flight demonstrated increased monocytes (P < .001) and reduced natural killer and B cells (P < .001). Circulating CD4 effector T cells decreased in patients who developed distant metastases (P = .049) but remained unchanged in recurrence-free patients. These effects were independent of tumor type and chemotherapy, indicating conserved immune changes following RT. CONCLUSIONS: We identified a distinct pattern of immune change across all tumor types analyzed in response to RT, with increases in protumoral myeloid cell populations, reductions in B cells and natural killer cells, and a significant decrease in CD4 effector T cells among patients who developed distant metastases.

论文信息

作者
Said BI、Boukhaled GM、Lok BH、Lukovic J、Mesci A、Waldron J、Wong P、Wang BX
第一作者单位
Princess Margaret Cancer Centre and University Health Network; Department of Radiation Oncology, University of Toronto.Canada
通讯作者单位
Princess Margaret Cancer Centre and University Health Network; Department of Radiation Oncology, University of Toronto; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: mike.milosevic@uhn.ca.Canada
文献类型
非美国政府资助研究
期刊
International journal of radiation oncology, biology, physics2026 Feb 1
原文标识
PubMed 40970850 · DOI 10.1016/j.ijrobp.2025.08.039