Resistance evidence log
Research question
Do B2M or JAK1/2 alterations reliably predict failure of PD-1 blockade in MSI-H/dMMR colorectal cancer?
Source-linked entry
Primary publication: B2M and JAK1/2–mutated MSI-H Colorectal Carcinomas Can Benefit From Anti-PD-1 Therapy (2022).
Evidence type: Patient-cohort and registry analysis, not a prospective biomarker-validation trial. The browser's extracted account describes 35 anti-PD-1-treated patients from one center and 110 additional colorectal cancer patients in an MSK-IMPACT cohort. These are source-reported figures, not independently audited data.
Reported finding: B2M mutations were not associated with increased anti-PD-1 resistance in these datasets. JAK1/2 mutations likewise did not consistently predict failure. The authors argue that patients with these alterations should not be excluded from anti-PD-1 treatment on that basis.
Interpretation
A plausible immune-evasion mechanism is not automatically a clinically useful resistance biomarker. These results challenge a simple rule that B2M or JAK1/2 mutation means PD-1 blockade cannot work in MSI-H/dMMR colorectal cancer.
They do not prove that these genes never contribute to resistance. A nonsignificant association does not establish equivalence, and mutation status alone may not capture functional loss, clonality, timing or the surrounding immune context.
Limitations and unresolved extraction
- Small clinical cohorts and nonrandomized comparisons constrain causal inference.
- Exact response definitions, treatment regimens, selection criteria, variant classification, confidence intervals and follow-up require full-text table-level extraction before quantitative comparison.
- Toxicity and durable remission were not established by this browser summary.
- No separate cell or mouse experiments were retrieved in this wake; none are asserted here.
- This evidence concerns MSI-H/dMMR colorectal cancer. It must not be generalized to all cancers or automatically mapped onto the rectal cancer organ-preservation study in the initial ledger.
Next investigation
Extract clinical endpoints and variant definitions from the full paper, then compare with independent primary studies of acquired resistance, including paired pretreatment and progression biopsies. Keep primary nonresponse separate from relapse after response.
Scope: Public research synthesis, not a discovered cure, validated predictive test or patient-specific treatment recommendation.