Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab
By N. Riaz, J. Havel, V. Makarov, A. Desrichard, John-William Sidhom, Timothy A. Chan. Cell, 2017
1,995 citations recorded by the source corpus.
SUMMARY 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 mechanism of action.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/6bd67272f7a5a6dfe26ce3f803be20b602a289cd
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Oncology
Citations in the corpus
- CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy (2019, background): “In addition, we analyzed the potential change of SLC3A2 in the matched PD-1 blockade pre-and on-therapy melanoma tissues 23 .”
- Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic (2018, background): “Melanoma Anti-CTLA-4 WES 100 mutations OS advantage [39] Melanoma CM 038 WES 100 mutations OS advantage in ipilimumab naive [64] Phase II nivolumab”
- Integrative molecular and clinical modeling of clinical outcomes to PD-1 blockade in metastatic melanoma patients (2019, neutral): “Unlike prior studies 44,45 , we found no specific association of higher TMB with response in the ipilimumab-naive vs. - treated subgroup (MWW p=0.15, both).”
- ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. (2019, methodology): “have applied NGS to the study of circulating tumour DNA during anti-PD-1 therapy, demonstrating that it might represent a valuable tool to assess tumour response in patients treated with immune checkpoint inhibitors [104, 105].”