{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:20:15Z","timestamp":1792808415204,"version":"4.5.0"},"reference-count":37,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Experimental Cancer Medicine Centre","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C22436\/A25354"],"award-info":[{"award-number":["C22436\/A25354"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CTUQQR-Dec22\/100006"],"award-info":[{"award-number":["CTUQQR-Dec22\/100006"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,12,1]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neutralization of interferon (IFN)-\u03b3 abrogates the efficacy of anti-programmed death-ligand 1 (PD-(L)1) checkpoint inhibitors. Most epithelial cells do not constitutively express major histocompatibility complex (MHC) class II but can be induced to do so by IFN-\u03b3. Inducible tumor-specific MHC class II (tsMHC-II) underlies responsiveness to anti-PD-(L)1. Retrospective studies show that tsMHC-II positivity associates with improved outcomes in patients treated with anti-PD-(L)1. The ANICCA-Class II single-arm Bayesian phase II trial prospectively explored whether positive tsMHC-II status could be a useful selection marker for anti-programmed cell death protein-1 (PD-1) in proficient mismatch repair colorectal cancer (pMMR CRC). In parallel, we retrospectively evaluated the potential predictive power of immunoscore-immune checkpoint (IS-IC) for outcome with single-agent immune checkpoint blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with histologically confirmed locally advanced\/metastatic pMMR CRC with &gt;1%\u2009MHC class II expression, Eastern Cooperative Oncology Group performance status 0\u20132, aged \u226518 years were eligible. Participants received 480\u2009mg nivolumab every 28 days for up to 24 cycles. The primary outcome was durable clinical benefit (DCB) defined as participants remaining progression-free at their third trial-specific scan since treatment start (ie, at approximately 27 weeks). Secondary outcomes included progression-free survival time (PFS) and overall survival time (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>35 participants were treated: 65.7% of participants\u2019 cancers were tsMHC-II \u22655%. 3\/35 patients achieved DCB (8.6%), estimating the true DCB rate (R) of 11% (95% credible interval 3% to 22%) with 0.002 probability that the true DCBR was &gt;30%, below the required 0.5 to warrant further research. The higher tsMHC-II cut-point \u22655% was not more useful in predicting duration of disease stabilization. All three participants who achieved DCB had no evidence of liver metastases (LM); DCBR 23.1% in those without versus 0% in those with LM. PFS and OS were significantly greater in those without LM. There was no evidence that IS-IC high predicted for prolonged time on treatment or improved tumor growth inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In pMMR CRC, tsMHC-II positivity fails to identify a subset of patients with metastatic pMMR CRC obtaining potentially meaningful benefit from single-agent anti-PD-1. Although numbers are limited, there is no clear evidence that IS-IC is predictive of outcome with single-agent anti-PD-1. The poor outcome in those with LM underscores the need for therapies that overcome the systemic immunosuppression driven by LM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012749","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T14:45:25Z","timestamp":1765982725000},"page":"e012749","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Final results of ANICCA-Class II, a single arm, open-label phase II trial assessing nivolumab in tissue-specific class II expressing metastatic microsatellite stable colorectal cancer, with a parallel assessment of the immunoscore-immune checkpoint as a predictive biomarker for single-agent 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