What question did this study set out to answer?

This research aims to investigate how particle radiotherapy influences tumor antigen presentation and T cell recruitment.

April 5, 2026

Abstract 2837: Enhanced tumor immune cell infiltration and antigen presentation after carbon ion radiotherapy correlates with curative outcomes

Key Points

This research aims to investigate how particle radiotherapy influences tumor antigen presentation and T cell recruitment.
Evaluated different ion types (protons, helium, carbon, oxygen) for their impact on immune priming.
Assessed MHC-I expression in human tumor cell lines and glioblastoma models using flow cytometry.
Utilized isogenic STING-KO cells to study the role of the cGAS-STING pathway.
Performed adoptive transfer of labeled T cells and tracked them using MRI.
Characterized TIL composition and immunity using single-cell RNA sequencing and mass cytometry.
MHC-I upregulation was found to be time-, dose-, and LET-dependent.
High LET carbon ion irradiation significantly increased MHC-I expression and T cell infiltration in tumors.
Enhanced intratumoral influx of T cells was confirmed through imaging techniques.
Modulating the quality of radiation treatment improved neoantigen expression and T cell recruitment.

Abstract

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. Citation Format: Matilde Recusani, Sarah Meister, Federica Ciamarone, Julian Schlegel, Ralph Sinn, Carmen Klein, Jennifer Furkel, Aoife Gahlawat, Christel Herold-Mende, Max Knoll, Michael Breckwoldt, Dirk Jaeger, Juergen Debus, Amir Abdollahi. Enhanced tumor immune cell infiltration and antigen presentation after carbon ion radiotherapy correlates with curative outcomes abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2837.

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Cite This Study

Recusani et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fdbfa79560c99a0a3fa8 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-2837

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