PO.IM01.04 · 免疫学

碳离子放射治疗后肿瘤免疫细胞浸润和抗原提呈增强与治愈性疗效相关

Enhanced tumor immune cell infiltration and antigen presentation after carbon ion radiotherapy correlates with curative outcomes

编号 2837 展板 10 时间 4/20 02:00–05:00 区域 Section 8 主讲 Matilde Recusani, MA

分会场 Immune Mechanisms Invoked by Other Therapies and Exposures

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作者与单位 Authors & Affiliations

Matilde Recusani¹, Sarah Meister¹, Federica Ciamarone¹, Julian Schlegel¹, Ralph Sinn², Carmen Klein³, Jennifer Furkel¹, Aoife Gahlawat¹, Christel Herold-Mende⁴, Max Knoll¹, Michael Breckwoldt², Dirk Jaeger⁵, Juergen Debus⁶, Amir Abdollahi¹

¹Translational Molecular Radiooncology, DKFZ, Heidelberg, Germany,²Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany,³Translational Radiation Oncology, NCT, Heidelberg, Germany,⁴Neurosurgical Research, University Hospital Heidelberg, Heidelberg, Germany,⁵Dir., Dept. of Medical Onc., Heidelberg University Hospital (UKHD), Heidelberg, Germany,⁶Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany

摘要 Abstract

中文摘要

免疫细胞浸润有限以及新表位和肿瘤相关抗原（TAA）经主要组织相容性复合体I类（MHC-I）提呈的缺陷，是有效免疫治疗的关键障碍。本研究探讨粒子放射治疗（RT）是否能够调节肿瘤抗原提呈和T细胞募集。通过评估质子、氦离子、碳离子和氧离子，我们评估了不同的生物物理特性——尤其是电离密度（线性能量传递，LET）——如何影响免疫启动。为此，我们评估了一组全面的人肿瘤细胞系（CaSki、SK-MEL-37、A549、PC3、LNCaP）以及同基因C57BL/6小鼠中的B16-F1黑色素瘤、GL261和005基因工程胶质母细胞瘤模型中MHC-I表达的诱导。流式细胞术显示MHC-I上调具有时间、剂量和LET依赖性。使用同基因STING-KO B16细胞证实了cGAS-STING通路的作用，这些细胞表现出RT诱导的MHC-I表达减少。在体内，高LET碳离子照射（CIRT）导致肿瘤MHC-I表达增强以及CD3⁺和CD8+ T细胞的瘤内浸润增加。过继转移超顺磁性氧化铁纳米颗粒（"SPION"）标记的T细胞，随后进行高场MRI示踪，证实了在分次（5 × 3 Gy）和单次超高剂量率（uHDR，FLASH）CIRT后瘤内流入增强。使用单细胞RNA测序和质谱流式细胞术（CyTOF）进一步表征了肿瘤浸润淋巴细胞（TIL）组成和免疫记忆。总的来说，这些数据表明，调节RT品质能够改善新抗原表达、MHC-I提呈和T细胞募集，凸显了粒子放射治疗重编程肿瘤免疫微环境的潜力。

查看英文原文 English abstract

Limited immune cell infiltration and deficient presentation of neoepitopes and tumor-associated antigens (TAA) via major histocompatibility complex class I (MHC-I) represent key barriers to effective immunotherapy. This study investigates whether particle radiotherapy (RT) can modulate tumor antigen presentation and T cell recruitment. By evaluating protons, helium, carbon, and oxygen ions, we assessed how distinct biophysical properties-particularly ionization density (linear energy transfer, LET)-influence immune priming. To this end, we evaluated the induction of MHC-I expression in a comprehensive panel of human tumor cell lines (CaSki, SK-MEL-37, A549, PC3, LNCaP), as well as in B16-F1 melanoma, GL261 and 005 genetically engineered glioblastoma models in syngeneic C57BL/6 mouse. Flow cytometry revealed MHC-I upregulation is time-, dose-, and LET-dependent. The role of the cGAS-STING pathway was confirmed using isogenic STING-KO B16 cells, which exhibited reduced RT-induced MHC-I expression. In vivo, high-LET carbon ion irradiation (CIRT) resulted in enhanced tumor MHC-I expression and increased intratumoral infiltration of CD3⁺ and CD8+ T cells. Adoptive transfer of Superparamagnetic Iron Oxide Nanoparticles (“SPION”)-labeled T cells, followed by high-field MRI tracing, confirmed enhanced intratumoral influx after fractionated (5 × 3 Gy) and single ultra-High Dose Rate (uHDR, FLASH) CIRT. Further characterization of tumor-infiltrating lymphocyte (TIL) composition and immunological memory was performed using single-cell RNA sequencing and mass cytometry (CyTOF). Collectively, these data indicate that modulating RT quality can improve neoantigen expression, MHC-I presentation, and T cell recruitment, highlighting the potential of particle radiotherapy to reprogram the tumor immune microenvironment.

利益披露 Disclosure

M. Recusani, None.. S. Meister, None.. F. Ciamarone, None.. J. Schlegel, None.. R. Sinn, None.. C. Klein, None.. J. Furkel, None.. A. Gahlawat, None.. C. Herold-Mende, None.. M. Knoll, None.. M. Breckwoldt, None.. J. Debus, None.. A. Abdollahi, None.

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