Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer

Nitin Roper, Moises J. Velez, Alberto Chiappori, Yoo Sun Kim, Jun S. Wei, Sivasish Sindiri, Nobuyuki Takahashi, Deborah Mulford, Suresh Kumar, Kris Ylaya, Christopher Trindade, Irena Manukyan, Anna-Leigh Brown, Jane B. Trepel, Jung-Min Lee, Stephen Hewitt, Javed Khan and Anish Thomas ()
Additional contact information
Nitin Roper: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH
Moises J. Velez: University of Rochester
Alberto Chiappori: Moffitt Cancer Center
Yoo Sun Kim: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH
Jun S. Wei: Center for Cancer Research, NCI, NIH
Sivasish Sindiri: Center for Cancer Research, NCI, NIH
Nobuyuki Takahashi: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH
Deborah Mulford: University of Rochester
Suresh Kumar: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH
Kris Ylaya: Center for Cancer Research, NCI, NIH
Christopher Trindade: Center for Cancer Research, NCI, NIH
Irena Manukyan: Center for Cancer Research, NCI, NIH
Anna-Leigh Brown: National Center for Biotechnology Information, NIH, NLM
Jane B. Trepel: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH
Jung-Min Lee: Center for Cancer Research, NCI, NIH
Stephen Hewitt: Center for Cancer Research, NCI, NIH
Javed Khan: Center for Cancer Research, NCI, NIH
Anish Thomas: Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24164-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24164-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24164-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().