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| Home > Publications database > Radiotherapy Upregulates the Expression of Membrane-Bound Negative Complement Regulator Proteins on Tumor Cells and Limits Complement-Mediated Tumor Cell Lysis. > print |
| Home > Publications database > Radiotherapy Upregulates the Expression of Membrane-Bound Negative Complement Regulator Proteins on Tumor Cells and Limits Complement-Mediated Tumor Cell Lysis. > print |
| 001 | 303228 | ||
| 005 | 20250731114306.0 | ||
| 024 | 7 | _ | |a 10.3390/cancers17142383 |2 doi |
| 024 | 7 | _ | |a pmid:40723265 |2 pmid |
| 037 | _ | _ | |a DKFZ-2025-01579 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Liang, Yingying |0 P:(DE-HGF)0 |b 0 |e First author |
| 245 | _ | _ | |a Radiotherapy Upregulates the Expression of Membrane-Bound Negative Complement Regulator Proteins on Tumor Cells and Limits Complement-Mediated Tumor Cell Lysis. |
| 260 | _ | _ | |a Basel |c 2025 |b MDPI |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1753941107_19394 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:E055#LA:E055# |
| 520 | _ | _ | |a Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types. |
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| 650 | _ | 7 | |a CD20 |2 Other |
| 650 | _ | 7 | |a DNA-damage repair |2 Other |
| 650 | _ | 7 | |a complement activation |2 Other |
| 650 | _ | 7 | |a complement-dependent cytotoxicity (CDC) |2 Other |
| 650 | _ | 7 | |a membrane-bound complement regulatory proteins (mCRPs) |2 Other |
| 650 | _ | 7 | |a radiosensitivity |2 Other |
| 650 | _ | 7 | |a radiotherapy |2 Other |
| 650 | _ | 7 | |a timing |2 Other |
| 700 | 1 | _ | |a Mai, Lixin |0 P:(DE-He78)4eba3fd5702e3a245f0b304e53203b2a |b 1 |u dkfz |
| 700 | 1 | _ | |a Schneeweiss, Jonathan |0 P:(DE-He78)117dc9df1284caf647d139cc91469e77 |b 2 |u dkfz |
| 700 | 1 | _ | |a Lopez Perez, Ramon |0 P:(DE-He78)c5a1a98649a7874de0def093eb136262 |b 3 |u dkfz |
| 700 | 1 | _ | |a Kirschfink, Michael |b 4 |
| 700 | 1 | _ | |a Huber, Peter |0 P:(DE-He78)3291aaac20f3d603d96744c1f0890028 |b 5 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.3390/cancers17142383 |g Vol. 17, no. 14, p. 2383 - |0 PERI:(DE-600)2527080-1 |n 14 |p 2383 |t Cancers |v 17 |y 2025 |x 2072-6694 |
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