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

IF 6.5 1区医学 Q1 ONCOLOGY

International Journal of Radiation Oncology Biology Physics Pub Date : 2025-09-19 DOI:10.1016/j.ijrobp.2025.08.039

Badr Id Said, Giselle M Boukhaled, Benjamin H Lok, Jelena Lukovic, Aruz Mesci, John Waldron, Philip Wong, Ben X Wang, David G Brooks, Michael Milosevic

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引用次数: 0

Abstract

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.

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交叉肿瘤分析揭示了治疗性放射治疗期间免疫调节的独特模式。

目的：放射治疗（RT）是根治性癌症治疗的基石，但其免疫效果尚不完全清楚。本研究检查了接受实体瘤放疗的患者的全身免疫谱变化。方法与材料：采用根治性放射治疗（bbb45 Gy， 1.8 ~ 3 Gy/分）的局限性头颈部癌、非小细胞肺癌、直肠癌、肢体软组织肉瘤患者。基线和放疗后（45 Gy后）血液样本使用多重Luminex细胞因子测定和高维质量细胞术（飞行时间细胞术）进行分析。免疫改变与患者预后相关。结果：37例头颈癌（n = 8）、非小细胞肺癌（n = 8）、直肠癌（n = 7）和软组织肉瘤（n = 14）患者接受了根治性放疗。大约50%的患者同时接受化疗。在中位随访21个月时，有3例局部复发，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 = 0.044）和单核细胞趋化蛋白-1 （P < 0.001）增加，它们在单核细胞运输和动员中都很重要。与细胞因子的变化一致，飞行时间测定显示单核细胞增加（P < 0.001），自然杀伤细胞和B细胞减少（P < 0.001）。在发生远处转移的患者中，循环CD4效应T细胞减少（P = 0.049），但在无复发的患者中保持不变。这些效应与肿瘤类型和化疗无关，表明放疗后的免疫变化是保守的。结论：我们发现了一种独特的免疫变化模式，在所有肿瘤类型中分析了对放疗的反应，在远处转移的患者中，原瘤髓细胞数量增加，B细胞和自然杀伤细胞减少，CD4效应T细胞显著减少。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Radiation Oncology Biology Physics 医学-核医学

CiteScore

11.00

自引率

7.10%

发文量

2538

审稿时长

6.6 weeks

期刊介绍： International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field. This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.