TY - JOUR
T1 - Combining ablative radiotherapy and anti CD47 monoclonal antibody improves infiltration of immune cells in tumor microenvironments
AU - Rostami, Elham
AU - Bakhshandeh, Mohsen
AU - Ghaffari-Nazari, Haniyeh
AU - Alinezhad, Maedeh
AU - Alimohammadi, Masoumeh
AU - Alimohammadi, Reza
AU - Mahmoodi Chalbatani, Ghanbar
AU - Hejazi, Ehsan
AU - Webster, Thomas J
AU - Tavakkol-Afshari, Jalil
AU - Jalali, Seyed Amir
N1 - Funding: 1. Mr Jalil Tavakkol-Afshari, Grant number:960553, Funder name: Mashhad University of Medical Sciences, URL: https://www. mums.ac.ir/index.php/en/ 2. Mr Seyed Amir Jalali, Grant number:97000722, Funder name: Iran National Science Foundation, URL: https://insf.org/ en The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2022/8/26
Y1 - 2022/8/26
N2 - Radiotherapy as an anti-tumor treatment can stimulate the immune system. However, irradiated tumor cells express CD47 to escape the anti-tumor immune response. Anti- CD47 Immunotherapy is a possible way to tackle this problem. This study evaluated the effect of single high dose radiotherapy combined with an anti-CD47 monoclonal antibody (αCD47 mAb) in CT26 tumor-bearing BALB/c mice. We assessed the tumors volume and survival in mice 60 days after tumor implantation. Also, immune cell changes were analyzed by flow cytometry in tumors, lymph nodes, and spleen. Combination therapy enhanced the anti-tumor response in treated mice by increasing CD8+ T cells and M1 macrophages and decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME). Also, our results showed that combination therapy increased survival time in mice compared to other groups. Furthermore, tumor volumes remarkably decreased in mice that received a single high dose RT plus αCD47 mAb. In conclusion, we showed that combining RT and αCD47 mAb improved the immune cell population in TME, regressed tumor growth, and increased survival in tumor-bearing mice.
AB - Radiotherapy as an anti-tumor treatment can stimulate the immune system. However, irradiated tumor cells express CD47 to escape the anti-tumor immune response. Anti- CD47 Immunotherapy is a possible way to tackle this problem. This study evaluated the effect of single high dose radiotherapy combined with an anti-CD47 monoclonal antibody (αCD47 mAb) in CT26 tumor-bearing BALB/c mice. We assessed the tumors volume and survival in mice 60 days after tumor implantation. Also, immune cell changes were analyzed by flow cytometry in tumors, lymph nodes, and spleen. Combination therapy enhanced the anti-tumor response in treated mice by increasing CD8+ T cells and M1 macrophages and decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME). Also, our results showed that combination therapy increased survival time in mice compared to other groups. Furthermore, tumor volumes remarkably decreased in mice that received a single high dose RT plus αCD47 mAb. In conclusion, we showed that combining RT and αCD47 mAb improved the immune cell population in TME, regressed tumor growth, and increased survival in tumor-bearing mice.
KW - Animals
KW - Antibodies, Monoclonal
KW - Antineoplastic Agents
KW - Cell Line, Tumor
KW - Mice
KW - Mice, Inbred BALB C
KW - Tumor Microenvironment
UR - https://pubmed.ncbi.nlm.nih.gov/36018888
U2 - 10.1371/journal.pone.0273547
DO - 10.1371/journal.pone.0273547
M3 - Article
C2 - 36018888
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0273547
ER -