{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:48:49Z","timestamp":1777009729414,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472083"],"award-info":[{"award-number":["82472083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the clinical significance and peripheral immunological basis underlying the dynamic changes of Gustave Roussy Immune (GRIm) score and the hepatocellular carcinoma\u2010specific GRIm (HCC\u2010GRIm) score in unresectable hepatocellular carcinoma (uHCC) patients treated with transarterial chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and antivascular endothelial growth factor (anti\u2010VEGF) antibodies or tyrosine kinase inhibitors (TKIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2010center retrospective study included uHCC patients treated with TACE combined with ICIs and anti\u2010VEGF antibodies or TKIs between July 2019 and August 2024. Primary outcomes were the objective response rate (ORR) and disease control rate (DCR), assessed at the first treatment evaluation at the end of the fourth cycle based on mRECIST criteria; secondary outcomes included overall survival (OS) and progression\u2010free survival (PFS). GRIm and HCC\u2010GRIm scores were calculated at four key timepoints: baseline (Cycle 0), second cycle (Cycle 2), fourth cycle (Cycle 4), and disease progression (PD). Their distributions and trajectory patterns were analyzed in relation to OS. Peripheral immune markers were measured at each timepoint to characterize immune response dynamics. Comparisons of immune marker levels and trends were performed between GRIm high and low score groups, as well as between objective responders (OR) and nonresponders (nOR) across treatment stages. Principal component analysis (PCA) was applied to derive an integrated immune\u2010metabolic index (PC1) from GRIm components, and its correlations with immune markers were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 68 uHCC patients treated with TACE plus ICIs and anti\u2010VEGF antibodies\/TKIs were included. At the first evaluation, the ORR was 52.9% and the DCR 86.8%. After a median follow\u2010up of 18.4\u2009months, the cohort showed a median overall survival (mOS) of 30.1\u2009months and a median progression\u2010free survival (mPFS) of 10.6\u2009months. GRIm and HCC\u2010GRIm scores remained stable across treatment phases, with their prognostic value for OS confined to baseline (Cycle 0) assessment (GRIm:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011; HCC\u2010GRIm:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Patients with persistently low scores had significantly longer OS than those with increasing trajectories (GRIm:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025; HCC\u2010GRIm:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048). Following treatment initiation, Ig\u03bb (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), Ig\u03ba (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), IgG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and IgA (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) levels showed an overall upward trend. At the first evaluation, these markers were significantly elevated in OR compared to baseline (Ig\u03bb [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022], Ig\u03ba [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032], IgG [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036], IgA [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019]), whereas no significant changes were observed in nOR (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). Among all timepoints, significant differences between high and low GRIm score groups were noted only at baseline, with higher Ig\u03bb (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), Ig\u03ba (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014), and IgG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009) levels in the high\u2010score group. In patients with low GRIm scores, linear regression revealed increasing trends in Ig\u03bb (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.042), Ig\u03ba (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017), and IgG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019) during treatment. PCA showed PC1 correlated positively with Ig\u03bb (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.259,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033), Ig\u03ba (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.293,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015), IgG (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.355,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), and complement factor B (CFB;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.314,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The GRIm and HCC\u2010GRIm scores were shown to be effective prognostic indicators only at baseline in uHCC patients treated with TACE combined with ICIs and anti\u2010VEGF antibodies or TKIs. Patients with low GRIm scores demonstrated treatment\u2010associated increases in Ig\u03bb, Ig\u03ba, and IgG levels. Ig\u03bb, Ig\u03ba, and IgG represent measurable links between GRIm\u2010defined risk categories, immune activation following treatment, and clinical outcomes. Integration of GRIm dynamics and immunoglobulin monitoring into clinical workflows may enhance risk stratification and support personalized treatment strategies in advanced HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71793","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:51:57Z","timestamp":1776401517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Monitoring of\n                    <scp>GRIm<\/scp>\n                    and\n                    <scp>HCC<\/scp>\n                    \u2010\n                    <scp>GRIm<\/scp>\n                    Scores Reveals Immunologically Relevant Prognostic Indicators in Hepatocellular Carcinoma Undergoing\n                    <scp>TACE<\/scp>\n                    Plus\n                    <scp>ICIs<\/scp>\n                    and Anti\u2010\n                    <scp>VEGF<\/scp>\n               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