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

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Listed:
  • Akash Mitra

    (University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences)

  • Miles C. Andrews

    (University of Texas MD Anderson Cancer Center
    La Trobe University)

  • 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
    University of Texas MD Anderson Cancer Center)

  • Cassian Yee

    (University of Texas MD Anderson Cancer Center
    Parker Institute for Cancer Immunotherapy)

  • 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
    University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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 , 2020. "Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15538-9
    DOI: 10.1038/s41467-020-15538-9
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