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Int Immunol. 2016 Aug;28(8):383-91. doi: 10.1093/intimm/dxw014. Epub 2016 Mar 17.

Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment.

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Department of Pathology, The University of Chicago, GCIS W423H, Chicago, IL 60637, USA


Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8(+) T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cell-inflamed tumors, exclusion of an anti-tumor specific T-cell infiltrate displays another even more potent mechanism of immune escape. This review will contrast the mechanisms of immunogenic, T-cell-inflamed, and the novel concept of non-immunogenic, non-T-cell-inflamed, adaptive immune escape.


checkpoint blockade; immune evasion; immunotherapy; oncogenes

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