In:
Journal of Immunotherapy, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 4 ( 2022-05), p. 187-193
Abstract:
β2-microglobulin ( B2M ) and Janus kinases 1 and 2 ( JAK1/2 ) mutations have been suggested as genetic mechanisms of immune evasion for anti–programmed cell death protein 1 (PD-1) therapy. Whether B2M and JAK 1/2 lose-of-function mutation can cause primary resistance to anti-PD-1 therapy in colorectal carcinoma (CRC) patients remains controversial. Here, we sought to compare the efficacy of anti-PD-1 therapy in DNA mismatch repair deficient/microsatellite instability–high CRC patients with or without B2M or JAK1/2 mutations. Thirty-Five CRC patients who received anti-PD-1 therapy were enrolled in this study. All tumor samples underwent next-generation sequencing. The clinical and molecular data from 110 CRC patients sequenced with the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay and accessed through cBioportal were also analyzed in this study. Of the 35 CRC patients from our center, 10 (28.6%) had a B2M loss-of-function mutation, and 8 (22.9%) had a JAK1/2 loss-of-function mutation. Compared with B2M wild-type CRCs, B2M -mutated CRCs did not show a higher frequency of resistance to anti-PD-1 therapy ( P =0.71). There was even better response to anti-PD-1 therapy in patients with JAK1/2 mutation than in those without ( P =0.015). Of the 110 CRC patients in the MSK-IMPACT datasets, 13 (11.8%) had a B2M mutation, and 15 (13.6%) had a JAK1/2 mutation. After analyzing the response to anti-PD-1 therapy in these 110 patients, we found similar results ( P =0.438 and 0.071, respectively). Moreover, patients with B2M or JAK1/2 mutation had a lower tumor mutational burden score compared with those without. B2M and JAK1/2 loss-of-function mutations occur frequently in microsatellite instability–high CRC. Our study demonstrated that patients with CRC harboring B2M or JAK1/2 mutations should not be excluded from anti-PD-1 therapy.
Type of Medium:
Online Resource
ISSN:
1524-9557
DOI:
10.1097/CJI.0000000000000417
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2048797-6
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