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Type III IFN (\u03bb), related to type I IFN (\u03b1), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-\u03bb on the tumor immune microenvironment have not been thoroughly investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-\u03bb3, and transduced tumor cells to evaluate the antitumor action of IFN-\u03bb3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-\u03bb3 in human bladder cancer and correlate it with immune cells\u2019 infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-\u03bb3 expression and the pathological complete response rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In immune-proficient tumors, ectopic\n                      <jats:italic>Ifnl3<\/jats:italic>\n                      expression in tumor cells significantly increased the infiltration of cytotoxic CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-\u03bb3 activity sensitized immune-proficient tumors to anti-PD-1\/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G\n                      <jats:sup>\u2013<\/jats:sup>\n                      Ly6C\n                      <jats:sup>+<\/jats:sup>\n                      I-A\/I-E\n                      <jats:sup>+<\/jats:sup>\n                      macrophages still enhanced tumor cell phagocytosis in\n                      <jats:italic>Ifnl3<\/jats:italic>\n                      overexpressing tumors. IFN-\u03bb3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-\u03bb3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study indicated that IFN-\u03bb3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-007808","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T13:26:00Z","timestamp":1712582760000},"page":"e007808","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Type III 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