Mismatch-repair deficiency is a predictive biomarker in solid tumors treated with PD-1 immune checkpoint blockade


Immune checkpoint blockade has the potential to achieve long-term benefit for patients. Although PD-L1 is a biomarker for immunotherapy, the response rate of this therapy is limited. The development of predictive biomarkers is needed in clinical practice. Solid tumors with mismatch-repair (MMR) deficiency is correlated with high numbers of somatic mutations that may be a predictive biomarker for immune recognition. A previous study showed colorectal cancer patients with MMR deficiency received immune checkpoint blockade have significant positive effects on the responses. In this study, scientists discovered durable clinical response of PD-1 immune checkpoint blockade in 87 patients across 12 different tumor types with MMR deficiency. The objective radiographic response rate is 53%, and 21% achieve complete radiographic response. The median progression-free survival (PFS) and median overall survival (OS) have not yet been reached. Furthermore, deep sequencing of TCR CDR3 regions (TCRseq) is used to identify the T cell clones in three patients. The data shows that the mutation-associated neoantigen T cell clones are correlated with the mutations found in the tumor. Taken together, this data reveals that patients with high mutation burden in their tumors, for example, tumor with MMR deficiency, benefited from immunotherapy.

Le DT, Durham JN1, Smith KN, et al., Science, 2017

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