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Despite advances in surgery, chemotherapy, targeted therapy, and immune checkpoint inhibitor (ICI)\u2010based regimens, durable disease control remains limited by primary or acquired resistance and marked biological heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>Immunotherapy, primarily based on ICIs, has shown clinical potential for advanced ICC; however, its activity is constrained by a highly immunosuppressive tumour microenvironment (TME), including desmoplastic stromal barriers, myeloid\u2010cell\u2010mediated suppression, impaired antigen presentation, cytokine\u2010 and chemokine\u2010driven immune exclusion, and metabolic remodeling. This review summarizes the tumour immune microenvironment (TIME) of ICC, with emphasis on cellular crosstalk among stromal, myeloid, and lymphoid compartments, extracellular matrix remodeling, metabolic constraints, and immune\u2010escape processes. We critically appraised first\u2010line chemoimmunotherapy evidence from advanced biliary tract cancer (BTC) trials and interpreted its relevance to ICC according to clinical evidence, tumour location, molecular subtype, and biomarker context. Biomarkers are discussed according to their current level of clinical validation, and molecular alterations, such as FGFR2 fusions, IDH1 mutations, and BAP1\/ARID1A alterations, are considered in relation to immune phenotypes and mechanism\u2010guided combination hypotheses. Finally, we evaluated emerging approaches, including next\u2010generation checkpoint inhibitors, antibody\u2013drug conjugates, bispecific antibodies, CAR\u2010T\/CAR\u2010macrophage (CAR\u2010M)\/CAR\u2010natural killer (CAR\u2010NK) cell therapies, cancer vaccines, and dendritic cell\u2010based interventions, with particular attention paid to antigen heterogeneity, stromal trafficking barriers, manufacturing complexity, and the limited maturity of ICC\u2010specific clinical evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>By integrating the mechanism, clinical evidence, molecular subtype and translational limitations, this review provides a balanced framework for biomarker\u2010guided precision immunotherapy in ICC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The clinical evidence and limitations of immunotherapy for intrahepatic cholangiocarcinoma are critically evaluated, with emphasis on ICC\u2010specific interpretation of broader biliary tract cancer trials.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The ICC tumour immune microenvironment is integrated into functional immune axes involving stromal, myeloid, lymphoid and metabolic regulation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Molecular subtypes and immune\u2010related biomarkers provide a framework for biomarker\u2010guided precision immunotherapy in ICC.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Current ICC immunotherapy trials remain limited by heterogeneous designs, small ICC\u2010specific cohorts and immature clinical evidence.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Emerging immunotherapies, including next\u2010generation checkpoint inhibitors, antibody\u2010drug conjugates, cellular therapies and vaccines, require ICC\u2010specific evaluation of biological barriers and clinical feasibility.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70830","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:39:42Z","timestamp":1789115982000},"source":"Crossref","is-referenced-by-count":0,"title":["Advances and challenges in immunotherapy for intrahepatic cholangiocarcinoma based on the tumour immune 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