What, Why, Where, and When: Bringing Timing to Immuno-Oncology

Adrienne M Rothschilds; K Dane Wittrup

doi:10.1016/j.it.2018.11.003

What, Why, Where, and When: Bringing Timing to Immuno-Oncology

Trends Immunol. 2019 Jan;40(1):12-21. doi: 10.1016/j.it.2018.11.003. Epub 2018 Dec 10.

Authors

Adrienne M Rothschilds¹, K Dane Wittrup²

Affiliations

¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: wittrup@mit.edu.

PMID: 30545676
DOI: 10.1016/j.it.2018.11.003

Abstract

A plethora of new cancer immunotherapies are under clinical development individually and in combination for a wide variety of indications, but optimizing therapeutic outcomes will require precise consideration of timing in treatment schedule design. In this review, we summarize the current understanding of the temporal rhythms of the anticancer immune response. Lessons learned in preclinical and clinical studies begin to define a framework for incorporating duration and sequencing into immunotherapy. We also discuss key challenges and opportunities for translation of temporally programmed treatment schedules to the clinic, including alignment of immunological timescales in preclinical models and humans, and the use of current and emerging biomarkers.

Keywords: CTLA-4; Immuno-oncology; Immunotherapy; PD-1; Timing.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / immunology*
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / immunology*
Humans
Neoplasms / drug therapy
Neoplasms / immunology*

Substances

Antineoplastic Agents
Biomarkers, Tumor