Table 3.
High-linear energy transfer (LET) radiation triggering immune responses.
| Biological System/Cell Type | Radiation Type | Immune Response | Ref. |
|---|---|---|---|
| Peripheral blood mononuclear cells (PBMCs) of head and neck (HNSCC) cancer patients | Intensity modulated radiotherapy (IMRT), (51–74 Gy total dose, 1.6–3 Gy dose/fraction) | Expression of the FXDR, SESN1, GADD45, DDB2, and MDM2 radiation-response genes were altered in the PBMCs of patients after RT. All changes were long-lasting, detectable one month after RT. Local tumor irradiation induces systemic changes in the level of immune and inflammation-related plasma proteins. RT induces changes in the immune phenotype of PBMCs of HNSCC patients. |
[168] |
| Murine CT26 colorectal cancer cells | 8 Gy proton beams at 1.09 keV/μm (low), 2.58 keV/μm (medium) and 7.7 keV/μm (high) LET. | Increase in percentage expression of immune markers (OX40L, CD40, ICAM-1, and MHC-I) in high-LET irradiated cells. High-LET proton radiation can be used to stimulate better immunogenic phenotype in tumor cells compared to low LET proton radiation. |
[169] |
| Human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr | Carbon ions (290 MeV/n, LET 30 keV/µm) | Carbon-ion beams significantly increased HMGB1 (a damage-associated molecular pattern—DAMP) levels in the culture supernatants. | [170] |
| NCI-H446 (lung tumor cells) | Carbon ions (290 MeV/n, LET 13 keV/µm) | Cyto- and chemokine response release by tumor cells after irradiation. (TNF-α) | [171] |
| Tumor-bearing mice (C3H/He, Balb/c nude mice) | Carbon ion irradiation (290 MeV/n, LET=77 keV/µm) | Increased cytotoxic T-lymphocytes (CTL)-associated lysis of isolated tumor splenocytes after carbon ion irradiation treatment with supplementary intratumoral dendritic cell (DC) injection. | [172] |
| Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice | Carbon ions (290 MeV/n, 6-cm spread-out Bragg peak, 6 Gy) | Even when exposed to the same equivalent doses, carbon ion therapy might activate the immune system to a greater extent than conventional RT. | [173] |
| NR-S1 and SCCVII (squamous cell carcinoma), NFSa, #8520 (fibrosarcoma) |
Carbon ions (290 MeV/n, LET 50 keV/µm) | Significant C-ion induced upregulation of stress-responsive and cell-communication genes common to different tumor types. | [174] |
| Rat skin | 56Fe ions (1.01 GeV/n) | 56Fe ion radiation significantly induced inflammation-related genes, including many in the categories of ‘immune response’, ‘response to stress’, ‘signal transduction’, and ‘response to biotic stress’, that contribute to carcinogenesis. | [175] |
| Highly aggressive HT1080 human fibrosarcoma and LM8 mouse osteosarcoma cells | Carbon ion beams (290 MeV/n), versus X-rays | When compared with photon irradiation, carbon ion exposure reduced the number of distant lung metastasis in carcinoma models in immunocompetent mice. | [176] |