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Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.

Publication ,  Journal Article
Wisdom, AJ; Mowery, YM; Hong, CS; Himes, JE; Nabet, BY; Qin, X; Zhang, D; Chen, L; Fradin, H; Patel, R; Bassil, AM; Muise, ES; King, DA ...
Published in: Nat Commun
December 17, 2020

Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy studies utilize transplant tumor models, which overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate immunoediting, decreased neoantigen expression, and tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors, revealing striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in both models, only transplant tumors are enriched for activated CD8+ T cells. The immune microenvironment of primary murine sarcomas resembles most human sarcomas, while transplant sarcomas resemble the most inflamed human sarcomas. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients with a sarcoma immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 17, 2020

Volume

11

Issue

1

Start / End Page

6410

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Tumor Escape
  • Single-Cell Analysis
  • Sarcoma
  • Programmed Cell Death 1 Receptor
  • Mice, Inbred Strains
  • Immunotherapy
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Exome Sequencing
 

Citation

APA
Chicago
ICMJE
MLA
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Wisdom, A. J., Mowery, Y. M., Hong, C. S., Himes, J. E., Nabet, B. Y., Qin, X., … Kirsch, D. G. (2020). Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy. Nat Commun, 11(1), 6410. https://doi.org/10.1038/s41467-020-19917-0
Wisdom, Amy J., Yvonne M. Mowery, Cierra S. Hong, Jonathon E. Himes, Barzin Y. Nabet, Xiaodi Qin, Dadong Zhang, et al. “Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.Nat Commun 11, no. 1 (December 17, 2020): 6410. https://doi.org/10.1038/s41467-020-19917-0.
Wisdom AJ, Mowery YM, Hong CS, Himes JE, Nabet BY, Qin X, et al. Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy. Nat Commun. 2020 Dec 17;11(1):6410.
Wisdom, Amy J., et al. “Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.Nat Commun, vol. 11, no. 1, Dec. 2020, p. 6410. Pubmed, doi:10.1038/s41467-020-19917-0.
Wisdom AJ, Mowery YM, Hong CS, Himes JE, Nabet BY, Qin X, Zhang D, Chen L, Fradin H, Patel R, Bassil AM, Muise ES, King DA, Xu ES, Carpenter DJ, Kent CL, Smythe KS, Williams NT, Luo L, Ma Y, Alizadeh AA, Owzar K, Diehn M, Bradley T, Kirsch DG. Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy. Nat Commun. 2020 Dec 17;11(1):6410.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 17, 2020

Volume

11

Issue

1

Start / End Page

6410

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Tumor Escape
  • Single-Cell Analysis
  • Sarcoma
  • Programmed Cell Death 1 Receptor
  • Mice, Inbred Strains
  • Immunotherapy
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Exome Sequencing