High somatic mutation and neoantigen burden do not correlate with decreased progression-free survival in hcc patients not undergoing immunotherapy

Angela Mauriello, Roberta Zeuli, Beatrice Cavalluzzo, Annacarmen Petrizzo, Maria Lina Tornesello, Franco M. Buonaguro, Michele Ceccarelli, Maria Tagliamonte, Luigi Buonaguro

Research output: Contribution to journalArticle

Abstract

Cancer genome instability leads to accumulation of mutations which may result into tumor-specific mutated “neoantigens”, not be affected by central T-cell tolerance. Such neoantigens are considered the optimal target for the patient’s anti-tumor T cell immunity as well as for personalized cancer immunotherapy strategies. However, only a minor fraction of predicted neoantigens are relevant to the clinical outcome. In the present study, a prediction algorithm was applied using datasets of RNA sequencing from all 377 Hepatocellular carcinoma (HCC) patients available at The Cancer Genome Atlas (TCGA), to predict neoantigens to be presented by each patient's autologous HLA molecules. Correlation with patients’ survival was performed on the 115 samples for whom the exact date of death was known. A total of 30 samples were used for the training set, and 85 samples were used for the validation sets. Neither the somatic mutations nor the number nor the quality of the predicted neoantigens correlate as single parameter with survival of HCC patients who do not undergo immunotherapy treatment. Furthermore, the preferential presentation of such neoantigens in the context of one of the major histocompatibility complex MHC class I molecules does not have an impact on the survival. On the contrary, the expression of Granzyme A (GZMA) is significantly correlated with survival and, in the context of high GZMA, a direct correlation between number and quality of neoantigens with survival is observed. This is in striking contrast to results described in cancer patients undergoing immunotherapy, in which a strong correlation between Tumor Mutational Burden (TMB), number of predicted neoantigens and survival has been reported.

Original languageEnglish
Article number1824
JournalCancers
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2019

    Fingerprint

Keywords

  • Cancer vaccine
  • Immunotherapy
  • Liver cancer
  • Neoantigens
  • Personalized treatment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mauriello, A., Zeuli, R., Cavalluzzo, B., Petrizzo, A., Tornesello, M. L., Buonaguro, F. M., Ceccarelli, M., Tagliamonte, M., & Buonaguro, L. (2019). High somatic mutation and neoantigen burden do not correlate with decreased progression-free survival in hcc patients not undergoing immunotherapy. Cancers, 11(12), [1824]. https://doi.org/10.3390/cancers11121824