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Open AccessArticle

Identification of 15 T Cell Restricted Genes Evaluates T Cell Infiltration of Human Healthy Tissues and Cancers and Shows Prognostic and Predictive Potential

1
Section of Pharmacology, Department of Medicine, University of Perugia, 06129 Perugia, Italy
2
Signal Transduction Laboratory, NIEHS, NIH, Department of Health and Human Services, Durham, NC 27709, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5242; https://doi.org/10.3390/ijms20205242
Received: 19 September 2019 / Revised: 17 October 2019 / Accepted: 21 October 2019 / Published: 22 October 2019
(This article belongs to the Special Issue Cancer Immunoediting and Beyond)
T cell gene signatures are used to evaluate T cell infiltration of non-lymphoid tissues and cancers in both experimental and clinical settings. However, some genes included in the available T cell signatures are not T cell-restricted. Herein, we propose a new human T cell signature that has been developed via a six-step procedure and comprises 15 T cell restricted genes. We demonstrate the new T cell signature, named signature-H, that differs from other gene signatures since it shows higher sensitivity and better predictivity in the evaluation of T cell infiltration in healthy tissues as well as 32 cancers. Further, results from signature-H are highly concordant with the immunohistochemistry methods currently used for assessing the prognosis of neuroblastoma, as demonstrated by the Kaplan–Meier curves of patients ranked by tumor T cell infiltration. Moreover, T cell infiltration levels calculated using signature-H correlate with the risk groups determined by the staging of the neuroblastoma. Finally, multiparametric analysis of tumor-infiltrating T cells based on signature-H let us favorably predict the response of melanoma to the anti-PD-1 antibody nivolumab. These findings suggest that signature-H evaluates T cell infiltration levels of tissues and may be used as a prognostic tool in the precision medicine perspective after appropriate clinical validation. View Full-Text
Keywords: tissue-resident memory T cells; T cell infiltration of human cancer; microarray; bioinformatics; precision medicine tissue-resident memory T cells; T cell infiltration of human cancer; microarray; bioinformatics; precision medicine
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MDPI and ACS Style

Cari, L.; De Rosa, F.; Petrillo, M.G.; Migliorati, G.; Nocentini, G.; Riccardi, C. Identification of 15 T Cell Restricted Genes Evaluates T Cell Infiltration of Human Healthy Tissues and Cancers and Shows Prognostic and Predictive Potential. Int. J. Mol. Sci. 2019, 20, 5242.

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