Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab
Paper by Shailender Bhatia indexed on Europe PMC as PubMed record 29033130, in Cell (2017), one of the most cited records naming an author with this name at Fred Hutchinson Cancer Center.
Overview
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab's mechanism of action.
Indexed on Europe PMC as PubMed record 29033130 (DOI 10.1016/j.cell.2017.09.028). Its author list gives "Bhatia S" with the affiliation "Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98105, USA", which names Fred Hutchinson Cancer Center; that is how the record was matched to Shailender Bhatia, and no figure has been checked by an editor.
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