Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma.
IF: 17.694
Cited by: 14


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.


Spatial Transcriptomics
Spatial Genomics

MeSH terms

Biomarkers, Tumor
DNA Copy Number Variations
Neutrophil Activation
Tumor Microenvironment


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

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