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• W2947713225 abstract "<h3>Background</h3> Insertion–deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. <h3>Case presentation</h3> Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of <i>TP53</i> and <i>PTEN</i> that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation <i>JAK2</i>, whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. <h3>Conclusions</h3> These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation." @default.
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• W2947713225 date "2019-05-07" @default.
• W2947713225 modified "2023-10-15" @default.
• W2947713225 title "Two cases of intrahepatic cholangiocellular carcinoma with high insertion-deletion ratios that achieved a complete response following chemotherapy combined with PD-1 blockade" @default.
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• W2947713225 doi "https://doi.org/10.1186/s40425-019-0596-y" @default.
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