Oncology Commons^™

Tumor And Microenvironment Evolution During Immunotherapy With Nivolumab., Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan

Articles, Abstracts, and Reports

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 …