# Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab

Source: https://onco.cc/key-papers/paper-shailender-bhatia-cell-2017/  
OnCo record `paper-shailender-bhatia-cell-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## 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'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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Cell
- Year: 2017
- DOI: 10.1016/j.cell.2017.09.028
- Authors: Riaz N, Havel JJ, Makarov V, et al.
- What it means: One of the most cited papers Europe PMC returns for Shailender Bhatia at Fred Hutchinson Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship.

## Sources

- Cell 2017: https://doi.org/10.1016/j.cell.2017.09.028
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29033130/
- Europe PMC: https://europepmc.org/article/MED/29033130

## Connected records

- people: [Shailender Bhatia](https://onco.cc/people/shailender-bhatia/)
- journals: [Cell](https://onco.cc/journals/cell/)

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