Differential Immune Modulation With Carbon-Ion Versus Photon Therapy

Spina, Catherine S.; Tsuruoka, Chizuru; Mao, Wendy; Sunaoshi, Masaaki; Chaimowitz, Matthew G.; Shang, Yi; Welch, David; Wang, Yifang; Venturini, Nicholas J.; Kakinuma, Shizuko; Drake, Charles G.

doi:10.1016/j.ijrobp.2020.09.053

Cited by 16 publications

(21 citation statements)

References 13 publications

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“…, evaluated the effects of carbon-ion therapy on immune modulation. They highlighted an interesting induction of pro-inflammatory cytokines 14 . Yoshimoto et al evaluated the immunogenic alterations induced by carbon ion irradiation in vitro.…”

Section: Introductionmentioning

confidence: 99%

Impact of proton therapy on antitumor immune response

Mirjolet

Nicol

Limagne

et al. 2021

Sci Rep

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Radiotherapy delivered using photons induces an immune response that leads to modulation of the tumor microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors in association with photon radiotherapy. At present, there is no publication on the radio-induced immune response after proton therapy. Balb/c mice bearing subcutaneous CT26 colon tumors were irradiated by a single fraction of 16.4 Gy using a proton beam extracted from a TR24 cyclotron. RNA sequencing analysis was assessed at 3 days post-treatment. Proton therapy immune response was monitored by flow cytometry using several panels (lymphoid, myeloid cells, lymphoid cytokines) at 7 and 14 days post-irradiation. RNA-Seq functional profiling identified a large number of GO categories linked to “immune response” and “interferon signaling”. Immunomonitoring evaluation showed induced tumor infiltration by immune cells. This is the first study showing the effect of proton therapy on immune response. These interesting results provide a sound basis to assess the efficacy of a combination of proton therapy and immune checkpoint inhibitors.

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Section: Introductionmentioning

confidence: 99%

Impact of proton therapy on antitumor immune response

Mirjolet

Nicol

Limagne

et al. 2021

Sci Rep

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“…However, due to the limitations of radiotherapy resistance, the immune synergy of radiotherapy needs to be further improved (36). Heavy ions have become definitive radiation therapy due to their superior radiobiological effects (23,37). However, the advantages and specific mechanisms of the immunogenic changes induced by heavy ions in dying tumor cells are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions

Ran

Wang

Dai

et al. 2021

Front. Public Health

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Increasing the immunogenicity of tumors is considered to be an effective means to improve the synergistic immune effect of radiotherapy. Carbon ions have become ideal radiation for combined immunotherapy due to their particular radiobiological advantages. However, the difference in time and dose of immunogenic changes induced by Carbon ions and X-rays has not yet been fully clarified. To further explore the immunogenicity differences between carbon ions and X-rays induced by radiation in different “time windows” and “dose windows.” In this study, we used principal component analysis (PCA) to screen out the marker genes from the single-cell RNA-sequencing (scRNA-seq) of CD8+ T cells and constructed a protein-protein interaction (PPI) network. Also, ELISA was used to test the exposure levels of HMGB1, IL-10, and TGF-β under different “time windows” and “dose windows” of irradiation with X-rays and carbon ions for A549, H520, and Lewis Lung Carcinoma (LLC) cell lines. The results demonstrated that different marker genes were involved in different processes of immune effect. HMGB1 was significantly enriched in the activated state, while the immunosuppressive factors TGF-β and IL-10 were mainly enriched in the non-functional state. Both X-rays and Carbon ions promoted the exposure of HMGB1, IL-10, and TGF-β in a time-dependent manner. X-rays but not Carbon ions increased the HMGB1 exposure level in a dose-dependent manner. Besides, compared with X-rays, carbon ions increased the exposure of HMGB1 while relatively reduced the exposure levels of immunosuppressive factors IL-10 and TGF-β. Therefore, we speculate that Carbon ions may be more advantageous than conventional X-rays in inducing immune effects.

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“…In this context, heavy-ion RT is of particular interest. Spina et al (21) and Simoniello et al (22) unambiguously demonstrated that CIRT could efficiently induce pro-inflammatory cytokines, while sparing circulating lymphocytes, which could polarize the tumor microenvironment into an antitumor one. For their physical selectivity, fewer chromosomal aberrations were described in patients treated with CIRT than with photon beam RT (23)(24)(25), leading to a higher number of available immune cells that might be recruited for the immune response after cancer (26).…”

Section: Immunomodulation Of the Tumor Microenvironmentmentioning

confidence: 99%

Hadrontherapy for Thymic Epithelial Tumors: Implementation in Clinical Practice

et al. 2021

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Radiation therapy is part of recommendations in the adjuvant settings for advanced stage or as exclusive treatment in unresectable thymic epithelial tumors (TETs). However, first-generation techniques delivered substantial radiation doses to critical organs at risk (OARs), such as the heart or the lungs, resulting in noticeable radiation-induced toxicity. Treatment techniques have significantly evolved for TET irradiation, and modern techniques efficiently spare normal surrounding tissues without negative impact on tumor coverage and consequently local control or patient survival. Considering its dosimetric advantages, hadrontherapy (which includes proton therapy and carbon ion therapy) has proved to be worthwhile for TET irradiation in particular for challenging clinical situations such as cardiac tumoral involvement. However, clinical experience for hadrontherapy is still limited and mainly relies on small-size proton therapy studies. This critical review aims to analyze the current status of hadrontherapy for TET irradiation to implement it at a larger scale.

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Differential Immune Modulation With Carbon-Ion Versus Photon Therapy

Cited by 16 publications

References 13 publications

Impact of proton therapy on antitumor immune response

Impact of proton therapy on antitumor immune response

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions

Hadrontherapy for Thymic Epithelial Tumors: Implementation in Clinical Practice

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