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Corrigendum
Open Access | 
10.1172/JCI185067
Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1
Callum Beach, David MacLean, Dominika Majorova, Stavros Melemenidis, Dhanya K. Nambiar, Ryan K. Kim, Gabriel N. Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily V.S. Hillson, Ashley K. McCulloch, Ross K. McMahon, Kathryn Pennel, Joanne Edwards, Sean M. O’Cathail, Campbell S. Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C. Koong, Trent M. Woodruff, Edward E. Graves, Tim Maughan, Simon J.A. Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J. Leedham, Amato J. Giaccia, and Monica M. Olcina
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Published August 15, 2024 - More info
J Clin Invest. 2024;134(16):e185067. https://doi.org/10.1172/JCI185067.
© 2024 Beach et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Related article:
Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1
Abstract
An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell–specific functions. C5aR1 targeting resulted in increased NF-κB–dependent apoptosis specifically in tumors and not normal tissues, indicating that, in malignant cells, C5aR1 primarily regulated cell fate. Collectively, these data revealed that increased complement gene expression is part of the stress response mounted by irradiated tumors and that targeting C5aR1 could improve radiotherapy, even in tumors displaying immunosuppressive features.
Authors
Callum Beach, David MacLean, Dominika Majorova, Stavros Melemenidis, Dhanya K. Nambiar, Ryan K. Kim, Gabriel N. Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily V.S. Hillson, Ashley K. McCulloch, Ross K. McMahon, Kathryn Pennel, Joanne Edwards, Sean M. O’Cathail, Campbell S. Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C. Koong, Trent M. Woodruff, Edward E. Graves, Tim Maughan, Simon J.A. Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J. Leedham, Amato J. Giaccia, Monica M. Olcina
Original citation: J Clin Invest. 2023;133(23):e168277. https://doi.org/10.1172/JCI168277
Citation for this corrigendum: J Clin Invest. 2024;134(16):e185067. https://doi.org/10.1172/JCI185067
During the preparation of this manuscript, the dose for PMX205 used for in vitro experiments was stated incorrectly in the legend for Figure 3A and in the Methods. In addition, the statement in Methods regarding staining for C5aR1 using the Leica BOND autostainer was incorrect. The correct sentences are below. The HTML and PDF files have been updated.
(A) HCT116 cells were treated with either vehicle or PMX205 (10 μg/mL) for 48 hours.
PMX205 treatment. For all in vitro experiments, cells were treated with 10 μg/mL PMX205 (Tocris, 5196) dissolved in 20% ethanol/water.
Proliferation assays. HCT116 or MC38 cells were seeded at the indicated concentration. Cells were treated with 10 μg/mL PMX205 (or RNAse-Free water as vehicle). On day 2, cells were counted using a hemocytometer and trypan blue in a 1:1 ratio. On day 3, 10 μg/mL PMX205 (or water) was added to the dishes.
C5aR1 (Abcam, catalog ab59390) was stained for chromogenically on the Leica BOND autostainer on a serial section.
The authors regret the errors.
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ISSN: 0021-9738 (print), 1558-8238 (online)