Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma

Akash Mitra, Miles C. Andrews, Whijae Roh, Marianna Petaccia Macedo, Courtney W. Hudgens, Fernando Carapeto, Shailbala Singh, Alexandre Reuben, Feng Wang, Xizeng Mao, Xingzhi Song, Khalida Wani, Samantha Tippen, Kwok-Shing Ng, Aislyn Schalck, Donald A. Sakellariou-Thompson, Eveline Chen, Sangeetha M. Reddy, Christine N. Spencer, Diana Wiesnoski, Latasha D. Little, Curtis Gumbs, Zachary A. Cooper, Elizabeth M. Burton, Patrick Hwu, Michael A. Davies, Jianhua Zhang, Chantale Bernatchez, Nicholas Navin, Padmanee Sharma, James P. Allison, Jennifer A. Wargo, Cassian Yee, Michael T. Tetzlaff, Wen-Jen Hwu, Alexander J. Lazar and P. Andrew Futreal ()
Additional contact information
Akash Mitra: University of Texas MD Anderson Cancer Center
Miles C. Andrews: University of Texas MD Anderson Cancer Center
Whijae Roh: The Broad Institute of MIT and Harvard
Marianna Petaccia Macedo: University of Texas MD Anderson Cancer Center
Courtney W. Hudgens: University of Texas MD Anderson Cancer Center
Fernando Carapeto: University of Texas MD Anderson Cancer Center
Shailbala Singh: University of Texas MD Anderson Cancer Center
Alexandre Reuben: University of Texas MD Anderson Cancer Center
Feng Wang: University of Texas MD Anderson Cancer Center
Xizeng Mao: University of Texas MD Anderson Cancer Center
Xingzhi Song: University of Texas MD Anderson Cancer Center
Khalida Wani: University of Texas MD Anderson Cancer Center
Samantha Tippen: University of Texas MD Anderson Cancer Center
Kwok-Shing Ng: University of Texas MD Anderson Cancer Center
Aislyn Schalck: University of Texas MD Anderson Cancer Center
Donald A. Sakellariou-Thompson: University of Texas MD Anderson Cancer Center
Eveline Chen: University of Texas MD Anderson Cancer Center
Sangeetha M. Reddy: University of Texas MD Anderson Cancer Center
Christine N. Spencer: Parker Institute for Cancer Immunotherapy
Diana Wiesnoski: University of Texas MD Anderson Cancer Center
Latasha D. Little: University of Texas MD Anderson Cancer Center
Curtis Gumbs: University of Texas MD Anderson Cancer Center
Zachary A. Cooper: AstraZeneca
Elizabeth M. Burton: University of Texas MD Anderson Cancer Center
Patrick Hwu: University of Texas MD Anderson Cancer Center
Michael A. Davies: University of Texas MD Anderson Cancer Center
Jianhua Zhang: University of Texas MD Anderson Cancer Center
Chantale Bernatchez: University of Texas MD Anderson Cancer Center
Nicholas Navin: University of Texas MD Anderson Cancer Center
Padmanee Sharma: University of Texas MD Anderson Cancer Center
James P. Allison: University of Texas MD Anderson Cancer Center
Jennifer A. Wargo: University of Texas MD Anderson Cancer Center
Cassian Yee: University of Texas MD Anderson Cancer Center
Michael T. Tetzlaff: University of Texas MD Anderson Cancer Center
Wen-Jen Hwu: University of Texas MD Anderson Cancer Center
Alexander J. Lazar: University of Texas MD Anderson Cancer Center
P. Andrew Futreal: University of Texas MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract Complex tumor microenvironmental (TME) features influence the outcome of cancer immunotherapy (IO). Here we perform immunogenomic analyses on 67 intratumor sub-regions of a PD-1 inhibitor-resistant melanoma tumor and 2 additional metastases arising over 8 years, to characterize TME interactions. We identify spatially distinct evolution of copy number alterations influencing local immune composition. Sub-regions with chromosome 7 gain display a relative lack of leukocyte infiltrate but evidence of neutrophil activation, recapitulated in The Cancer Genome Atlas (TCGA) samples, and associated with lack of response to IO across three clinical cohorts. Whether neutrophil activation represents cause or consequence of local tumor necrosis requires further study. Analyses of T-cell clonotypes reveal the presence of recurrent priming events manifesting in a dominant T-cell clonotype over many years. Our findings highlight the links between marked levels of genomic and immune heterogeneity within the physical space of a tumor, with implications for biomarker evaluation and immunotherapy response.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15538-9 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:11:y:2020:i:1:d:10.1038_s41467-020-15538-9

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

DOI: 10.1038/s41467-020-15538-9

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 ().