Potential synergistic effect of radiotherapy and immunotherapy shown in vitro on cancer cells
November 2016
National Institutes of Health, Bethesda, USA
Prostate cancer is one of the most prevalent malignancies among men worldwide. Castration-resistant prostate cancer (CRPC) has a high tendency to metastasize to bone. One treatment option for CRPC is a combination of radiotherapy and immunotherapy but it is currently unknown if radiation therapy can alter the phenotype of the surviving tumor cells in ways that render them more susceptible to cytotoxic T lymphocyte (CTL)-mediated attack. In the present study, the researchers exposed human prostate, breast, and lung carcinoma cells to sublethal doses of 223Ra radiotherapy in vitro. 223Ra significantly enhanced T cell-mediated lysis of each tumor type. Immunofluorescence analysis revealed that the increase in CTL killing was accompanied by augmented protein expression of molecules that are essential for efficient antigen presentation. The phenotypic changes observed after radiotherapy appear to be mediated by induction of the endoplasmic reticulum stress response pathway. By rendering tumor cells more susceptible to T cell-mediated lysis, 223Ra may potentially be effective in combination with various immunotherapies.
Sublethal exposure to alpha radiation (223Ra dichloride) enhances various carcinomas’ sensitivity to lysis by antigen-specific cytotoxic T lymphocytes through calreticulin-mediated immunogenic modulation
James W. Hodge
Added on: 09-19-2021
[1] https://www.oncotarget.com/article/13520/text/[2] https://data.jrc.ec.europa.eu/dataset/352f7dfd-05cf-434b-a96a-7e270dc76573
