{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:51:00Z","timestamp":1793163060584,"version":"4.5.0"},"reference-count":43,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000982","name":"Conquer Cancer Foundation","doi-asserted-by":"publisher","award":["0000043353"],"award-info":[{"award-number":["0000043353"]}],"id":[{"id":"10.13039\/100000982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,8,18]]},"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiotherapy (RT) has been shown to stimulate an antitumor immune response in irradiated tumors as well as unirradiated distant sites (abscopal effect). Previous studies have demonstrated a role for the tumor-draining lymph node (LN) in mediating an anti-programmed death-1 (PD-1)\/programmed death ligand-1 (PD-L1) stimulated antitumor immune response. Here, we investigated whether the LN is also important in mediating a RT alone stimulated abscopal response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a subcutaneous modified B16F10 flank tumor model injected bilaterally. Our B16F10 cell line has an inserted viral glycoprotein which facilitated identification of tumor-specific T-cells. RT was directed at one flank tumor alone or one flank tumor and the tumor-draining LN. We evaluated response by tumor growth measurements and flow cytometry of both tumor-infiltrating and LN T-cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that local tumor irradiation improves distant tumor control (abscopal effect). Depletion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells significantly reduced this abscopal response. We have previously shown, in a chronic lymphocytic choriomeningitis virus (LCMV) infection, that the T-cell proliferative burst following blockade of PD-1\/L1 is provided by a \u2018stem-like\u2019 CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subset which then differentiate into terminally differentiated effectors. These terminally differentiated effectors have the potential to kill virally infected or tumor cells following PD-1\/L1 blockade. In the chronic LCMV infection, stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells were found exclusively in secondary lymphoid organs. Similarly, here we found these cells at high frequencies in the tumor-draining LN, but at low frequencies within the tumor. The effect of RT on this T-cell subset in unknown. Interestingly, tumor irradiation stimulated total CD8\n                      <jats:sup>+<\/jats:sup>\n                      and stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell proliferation in the LN. When the LN and the tumor were then targeted with RT, the abscopal effect was reduced, and we found a concomitant reduction in the number of total tumor-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells and stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells in both the irradiated and unirradiated tumor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These correlative results suggest the tumor-draining LN may be an important mediator of the abscopal effect by serving as a stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell reservoir, a site for stem-like T-cell expansion, and a site from which they can populate the tumor.\n                    <\/jats:p>\n                  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