All is not lost: learning from 9p21 loss in cancer

Pavlina Spiliopoulou; S Y Cindy Yang; Jeff P Bruce; Ben X Wang; Hal K Berman; Trevor J Pugh; Lillian L Siu

doi:10.1016/j.it.2022.03.003

All is not lost: learning from 9p21 loss in cancer

Trends Immunol. 2022 May;43(5):379-390. doi: 10.1016/j.it.2022.03.003. Epub 2022 Apr 1.

Authors

Pavlina Spiliopoulou¹, S Y Cindy Yang¹, Jeff P Bruce¹, Ben X Wang¹, Hal K Berman², Trevor J Pugh³, Lillian L Siu⁴

Affiliations

¹ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
² Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Toronto General Hospital, University Health Network, Toronto, ON, Canada.
³ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada.
⁴ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: lillian.siu@uhn.ca.

PMID: 35379580
DOI: 10.1016/j.it.2022.03.003

Abstract

The cancer research community continues to search for additional biomarkers of response and resistance to immune checkpoint treatment (ICT). The ultimate goal is to direct the use of ICT in patients whose tumors are most likely to benefit to achieve a refinement that is equivalent to that of a genotype-matched targeted treatment. Dissecting the mechanisms of ICT resistance can help us characterize ICT nonresponders more efficiently. In this opinion, we argue that there may be additional knowledge gained about immune evasion in cancer by analyzing the loss of the human 9p21.3 locus; as an example, we highlight findings of 9p21.3 loss from the investigator-initiated, pan-cancer INSPIRE study, in which patients were treated with pembrolizumab (anti-PD-1 antibody) ICT.

Keywords: 9p21.3 loss; CDKN2A/B; MTAP; cancer immunotherapy; treatment resistance biomarkers; tumour microenvironment.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neoplasms* / drug therapy