The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival

Jing Zhang, Francesca P. Caruso, Jason K. Sa, Sune Justesen, Do Hyun Nam, Peter Sims, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Glioblastoma (GBM) is resistant to multimodality therapeutic approaches. A high burden of tumor-specific mutant peptides (neoantigens) correlates with better survival and response to immunotherapies in selected solid tumors but how neoantigens impact clinical outcome in GBM remains unclear. Here, we exploit the similarity between tumor neoantigens and infectious disease-derived immune epitopes and apply a neoantigen fitness model for identifying high-quality neoantigens in a human pan-glioma dataset. We find that the neoantigen quality fitness model stratifies GBM patients with more favorable clinical outcome and, together with CD8+ T lymphocytes tumor infiltration, identifies a GBM subgroup with the longest survival, which displays distinct genomic and transcriptomic features. Conversely, neither tumor neoantigen burden from a quantitative model nor the isolated enrichment of CD8+ T lymphocytes were able to predict survival of GBM patients. This approach may guide optimal stratification of GBM patients for maximum response to immunotherapy.

Original languageEnglish
Article number135
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Fingerprint

T-cells
Glioblastoma
Tumors
T-lymphocytes
T-Lymphocytes
neoplasms
Survival
immunotherapy
Tumor Burden
Immunotherapy
Neoplasms
transcriptomics
Infiltration
epitopes
infectious diseases
Epitopes
Glioma
Communicable Diseases
peptides
genomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival. / Zhang, Jing; Caruso, Francesca P.; Sa, Jason K.; Justesen, Sune; Nam, Do Hyun; Sims, Peter; Ceccarelli, Michele; Lasorella, Anna; Iavarone, Antonio.

In: Communications Biology, Vol. 2, No. 1, 135, 01.12.2019.

Research output: Contribution to journalArticle

Zhang, Jing ; Caruso, Francesca P. ; Sa, Jason K. ; Justesen, Sune ; Nam, Do Hyun ; Sims, Peter ; Ceccarelli, Michele ; Lasorella, Anna ; Iavarone, Antonio. / The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival. In: Communications Biology. 2019 ; Vol. 2, No. 1.
@article{b1b5f944d2aa4544923c1e1f7ac38132,
title = "The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival",
abstract = "Glioblastoma (GBM) is resistant to multimodality therapeutic approaches. A high burden of tumor-specific mutant peptides (neoantigens) correlates with better survival and response to immunotherapies in selected solid tumors but how neoantigens impact clinical outcome in GBM remains unclear. Here, we exploit the similarity between tumor neoantigens and infectious disease-derived immune epitopes and apply a neoantigen fitness model for identifying high-quality neoantigens in a human pan-glioma dataset. We find that the neoantigen quality fitness model stratifies GBM patients with more favorable clinical outcome and, together with CD8+ T lymphocytes tumor infiltration, identifies a GBM subgroup with the longest survival, which displays distinct genomic and transcriptomic features. Conversely, neither tumor neoantigen burden from a quantitative model nor the isolated enrichment of CD8+ T lymphocytes were able to predict survival of GBM patients. This approach may guide optimal stratification of GBM patients for maximum response to immunotherapy.",
author = "Jing Zhang and Caruso, {Francesca P.} and Sa, {Jason K.} and Sune Justesen and Nam, {Do Hyun} and Peter Sims and Michele Ceccarelli and Anna Lasorella and Antonio Iavarone",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s42003-019-0369-7",
language = "English",
volume = "2",
journal = "Communications Biology",
issn = "2399-3642",
number = "1",

}

TY - JOUR

T1 - The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival

AU - Zhang, Jing

AU - Caruso, Francesca P.

AU - Sa, Jason K.

AU - Justesen, Sune

AU - Nam, Do Hyun

AU - Sims, Peter

AU - Ceccarelli, Michele

AU - Lasorella, Anna

AU - Iavarone, Antonio

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Glioblastoma (GBM) is resistant to multimodality therapeutic approaches. A high burden of tumor-specific mutant peptides (neoantigens) correlates with better survival and response to immunotherapies in selected solid tumors but how neoantigens impact clinical outcome in GBM remains unclear. Here, we exploit the similarity between tumor neoantigens and infectious disease-derived immune epitopes and apply a neoantigen fitness model for identifying high-quality neoantigens in a human pan-glioma dataset. We find that the neoantigen quality fitness model stratifies GBM patients with more favorable clinical outcome and, together with CD8+ T lymphocytes tumor infiltration, identifies a GBM subgroup with the longest survival, which displays distinct genomic and transcriptomic features. Conversely, neither tumor neoantigen burden from a quantitative model nor the isolated enrichment of CD8+ T lymphocytes were able to predict survival of GBM patients. This approach may guide optimal stratification of GBM patients for maximum response to immunotherapy.

AB - Glioblastoma (GBM) is resistant to multimodality therapeutic approaches. A high burden of tumor-specific mutant peptides (neoantigens) correlates with better survival and response to immunotherapies in selected solid tumors but how neoantigens impact clinical outcome in GBM remains unclear. Here, we exploit the similarity between tumor neoantigens and infectious disease-derived immune epitopes and apply a neoantigen fitness model for identifying high-quality neoantigens in a human pan-glioma dataset. We find that the neoantigen quality fitness model stratifies GBM patients with more favorable clinical outcome and, together with CD8+ T lymphocytes tumor infiltration, identifies a GBM subgroup with the longest survival, which displays distinct genomic and transcriptomic features. Conversely, neither tumor neoantigen burden from a quantitative model nor the isolated enrichment of CD8+ T lymphocytes were able to predict survival of GBM patients. This approach may guide optimal stratification of GBM patients for maximum response to immunotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85071047399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071047399&partnerID=8YFLogxK

U2 - 10.1038/s42003-019-0369-7

DO - 10.1038/s42003-019-0369-7

M3 - Article

VL - 2

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 135

ER -