{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:40:38Z","timestamp":1793256038146,"version":"4.5.0"},"reference-count":58,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,15]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intratumoral vaccines offer a promising avenue in cancer immunotherapy by harnessing the tumor microenvironment to stimulate immune responses. However, challenges persist in maximizing their effectiveness and addressing immune suppression within tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Conventional in situ vaccine (CisVac) and \u03b1-CD137 antibody were administered in implanted mouse models of lung and colon cancer to evaluate therapeutic efficacy. The initiation mechanism of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells was determined using antibody blockade and transgenic mouse models. Single-cell RNA sequencing was used to further characterize the activation mechanism of T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that this synergistic approach markedly inhibits tumor growth while eliciting a robust antitumor immune response, characterized by heightened activation and cytotoxic differentiation of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, as well as the polarization of conventional dendritic cells (cDC1). Mechanistically, it promotes the cDC1-dependent proportion and cytokine production of tumor antigen-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, mobilizes and establishes enduring systemic immune memory. Our single-cell transcriptome analyses revealed that the therapy facilitates a functional remodeling of regulatory T cells (Tregs) with upregulated inflammatory genes, potentially attenuating immune suppression. Cell\u2013cell communication analyses highlighted interactions between CD4\n                      <jats:sup>+<\/jats:sup>\n                      Th1-like\/Th17 cells and monocytes\/DCs through the CD40L-CD40 pathway, indicating potential intercellular regulatory mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results highlight the transformative potential of the CisVac\/\u03b1-CD137 combination in cancer immunotherapy, paving the way for further exploration of its clinical utility and long-term efficacy.<\/jats:p>\n                  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