Beyond the tumor microenvironment: a hierarchical immune-circuit model of immune checkpoint blockade resistance
Xue Zhao, Han Wang, Yanan Liu, Lanqing Cao · 2026
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Description
Xue Zhao and three co-authors propose a circuit model of why immune checkpoint therapy fails in this 2026 paper. These drugs release the brakes on T cells and control some cancers for years. Resistance is usually blamed on the tumor or its immediate surroundings. The authors widen the frame to three nested levels: killing at the tumor, training in the draining lymph nodes, and calibration across the whole body. Failure at any level can starve the levels inside it.
They walk through resistance at each level and four feedback paths between them, across six cancer types. Evidence from animal tests, human tissue studies, and trials supports parts of the circuit, unevenly. The authors are careful: their model is a research hypothesis, not a care standard. Its worth will be proven only if measuring all three levels predicts outcomes better than tumor only models.
Catalog record
| CREATOR | Xue Zhao, Han Wang, Yanan Liu, Lanqing Cao |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 89 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |