Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing
Menée in vitro, cette étude montre que les cellules tumorales ayant résisté à des faisceaux de protons ou de photons expriment des antigènes qui augmentent leur sensibilité aux lymphocytes T cytotoxiques
Purpose : This study was designed to provide the foundation for combining immunotherapy to induce tumor antigen-specific T cells with proton radiation therapy to exploit the activity of those T cells. We have recently defined “immunogenic modulation,” a mechanism distinct from immunogenic cell death, whereby tumor cells surviving photon radiation therapy nonetheless become more susceptible to cytotoxic T lymphocyte (CTL)-mediated lysis. However, to our knowledge, there are no prior studies examining the role of proton radiation on tumor immune sensitivity. Materials and Methods : Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results : These studies show for the first time that a) proton and photon radiation induced comparable upregulation of surface molecules involved in immune recognition (HLA, ICAM-1, and the tumor-associated antigens CEA and MUC-1), b) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells, and c) cancer stem cells (CSCs), which are resistant to the direct cytolytic activity of proton radiation, nonetheless upregulated calreticulin after radiation in a manner similar to non-CSCs. Conclusions : These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.