Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23045
Title: Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma.
Austin Authors: Mitra, Akash;Andrews, Miles C;Roh, Whijae;De Macedo, Marianna Petaccia;Hudgens, Courtney W;Carapeto, Fernando;Singh, Shailbala;Reuben, Alexandre;Wang, Feng;Mao, Xizeng;Song, Xingzhi;Wani, Khalida;Tippen, Samantha;Ng, Kwok-Shing;Schalck, Aislyn;Sakellariou-Thompson, Donald A;Chen, Eveline;Reddy, Sangeetha M;Spencer, Christine N;Wiesnoski, Diana;Little, Latasha D;Gumbs, Curtis;Cooper, Zachary A;Burton, Elizabeth M;Hwu, Patrick;Davies, Michael A;Zhang, Jianhua;Bernatchez, Chantale;Navin, Nicholas;Sharma, Padmanee;Allison, James P;Wargo, Jennifer A;Yee, Cassian;Tetzlaff, Michael T;Hwu, Wen-Jen;Lazar, Alexander J;Futreal, P Andrew
Affiliation: Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Quantitative Sciences Graduate Training Program, Graduate School of Biomedical Sciences, Houston, Texas, USA
Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Institute for Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Parker Institute for Cancer Immunotherapy, San Francisco, California, USA
AstraZeneca, Gaithersburg, Maryland, USA
Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: 15-Apr-2020
metadata.dc.date: 2020-04-15
Publication information: Nature communications 2020; 11(1): 1839
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23045
DOI: 10.1038/s41467-020-15538-9
ORCID: 0000-0002-0633-1615
0000-0003-1231-8641
0000-0002-7395-9939
0000-0002-0434-7605
0000-0001-8312-7485
0000-0003-4510-0382
0000-0003-0364-7443
0000-0003-1059-0940
0000-0002-0977-0912
0000-0001-5412-9860
0000-0003-3438-7576
0000-0002-6395-4499
0000-0001-8663-2671
PubMed URL: 32296058
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

2
checked on Nov 30, 2020

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.