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Mouse Models for Immunotherapy in Hepatocellular Carcinoma
Open AccessArticle

High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy

1
Laboratory of Cancer Immunoregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori IRCCS, “Fondazione Pascale”, 80131 Naples, Italy
2
Science and Technology Dept, University del Sannio, 82100 Benevento, Italy
3
BIOGEM S.c.a.r.l., 83031 Ariano Iprino, Italy
4
Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale”-IRCCS, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(12), 1824; https://doi.org/10.3390/cancers11121824
Received: 5 September 2019 / Revised: 11 November 2019 / Accepted: 14 November 2019 / Published: 20 November 2019
(This article belongs to the Special Issue Models of Experimental Liver Cancer)
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. View Full-Text
Keywords: liver cancer; immunotherapy; cancer vaccine; personalized treatment; neoantigens liver cancer; immunotherapy; cancer vaccine; personalized treatment; neoantigens
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Mauriello, A.; Zeuli, R.; Cavalluzzo, B.; Petrizzo, A.; Tornesello, M.L.; Buonaguro, F.M.; Ceccarelli, M.; Tagliamonte, M.; Buonaguro, L. High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy. Cancers 2019, 11, 1824.

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