Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines

Abstract

While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-Db and H2-Kb was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.

Charged Particle Irradiation for Pancreatic Cancer: A Systematic Review of In Vitro Studies

“…The characteristics of included ( 13 – 15 , 18 – 34 ) studies are summarized in Table 1 . Briefly, 13 carbon ion irradiation and seven proton irradiation studies were included in our final SR; these studies were published between 2004 and 2021.They were conducted in 7 different countries: Japan, Germany, Belgium, Italy, Korea, the United States of America, and Lithuania.…”

“…Briefly, 13 carbon ion irradiation and seven proton irradiation studies were included in our final SR; these studies were published between 2004 and 2021.They were conducted in 7 different countries: Japan, Germany, Belgium, Italy, Korea, the United States of America, and Lithuania. Of these studies, almost all used human pancreatic cancer cell lines, such as AsPC-1, BxPc-3, MIA PaCa-2, PANC-1, and PK45, only one ( 18 ) used transgenic mice cell lines (PDA30364/OVA). The studies varied in the initial energy, averaged LET, SOBP, radiation doses, and dose rates used.…”

“…Four publications ( 19 , 25 , 28 , 33 ) only partly described how results were measured; the remaining 16 described these methods in detail. One study ( 23 ) did not mention the conditions in which cells were cultured, and four studies ( 18 , 31 , 33 , 34 ) partly reported the cell origin and cell type. Only one study ( 25 ) did not clear whether there was industry sponsoring; the rest were reported to have no connections with or employment at a company.…”

Modeling Radioimmune Response—Current Status and Perspectives

“…Also at the moment it is not clear whether or not high LET radiation will enhance the infiltration capability of T cells in the tumor microenvironment, or whether the latter will be modified in other aspects. First experimental results ( 78 – 80 ) do not show a clear picture yet, while the tissue sparing effect of particle irradiation indeed seems to be beneficial regarding lymphocyte deprivation ( 81 ). Thus the multiple perspectives and open questions associated with the use of high LET RIT warrant further preclinical experiments, which are able to answer the speculative and encouraging expectations presented above.…”

Biological Rationale and Clinical Evidence of Carbon Ion Radiation Therapy for Adenoid Cystic Carcinoma: A Narrative Review

“…Hartman et al ( 53 ) found in vitro that CIRT and photon beam radiotherapy had common radiobiological properties such as induction of cell cycle arrest, surface expression of immune-modulating molecules, and activation of cytotoxic lymphocytes. Nevertheless, other authors have suggested that CIRT-induced immune activation might be more potent.…”