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Their synergy mechanisms remain largely unknown. AL3810 (lucitanib), a AAMKI in Phase II trials, has demonstrated clinical activity. We aim to elucidate the immune modulatory effects of AL3810 and provide a rationale for its combination with immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Murine colorectal cancer models (CT26\/MC38) were used. Immunofluorescence\/histochemistry, flow cytometry and mass cytometry were used to explore the modulation of AL3810 alone or combined with anti\u2010PD\u20101 on the tumour microenvironment (TME). Myeloid antigen\u2010presenting cells (APCs) were sorted and co\u2010cultured with pre\u2010activated OT\u20101 CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells to evaluate their effect on CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Low\u2010dose AL3810 pruned aberrant vessels and increased pericyte coverage, whereas high\u2010dose caused severe hypoxia and reduced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell infiltration. Through CSF1R inhibition, low\u2010dose AL3810 reduced MHC\u2010II\n                      <jats:sup>int<\/jats:sup>\n                      tumour\u2010associated macrophages, which impaired the function and survival of TCF\u20101\n                      <jats:sup>\u2212<\/jats:sup>\n                      TIM\u20103\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells. Meanwhile it preserved MHC\u2010II\n                      <jats:sup>high<\/jats:sup>\n                      TAMs and conventional dendritic cells, which triggered TCF\u20101\n                      <jats:sup>+<\/jats:sup>\n                      TIM\u20103\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells differentiated into functionally stronger and more viable TCF\u20101\n                      <jats:sup>\u2212<\/jats:sup>\n                      TIM\u20103\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells. Consistently, the increased expansion and enhanced cytotoxic potential of TCF\u20101\n                      <jats:sup>\u2212<\/jats:sup>\n                      TIM\u20103\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells underpinned the synergistic antitumour efficacy of low\u2010dose AL3810 combined with \u03b1PD\u20101. Additionally, low\u2010dose AL3810 upregulated co\u2010stimulatory receptors on tumour\u2010infiltrating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells, providing potential targets to further optimize the regimen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      These findings indicate a novel immunomodulatory mechanism of low\u2010dose AL3810, indicating ability to reprogram APC\u2013CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell interactions, a critical axis of immune regulation, supporting its rational combination with PD\u20101 blockade in CRC treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70664","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:52:08Z","timestamp":1790661128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010dose antiangiogenic multikinase inhibitor AL3810 synergizes with PD\u20101 blockade by reducing CSF1\u2010driven MHC\u2010II\n                    <sup>int<\/sup>\n                    tumour\u2010associated macrophages to optimize TIM\u20103\n                    <sup>+<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    T\u2010cell effector function"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5753-7215","authenticated-orcid":false,"given":"Kun","family":"Fang","sequence":"first","affiliation":[{"name":"Division of Anti\u2010tumor Pharmacology Shanghai Institute of Materia Medica, Chinese Academy of Sciences  Shanghai 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