Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms20205242
Keywords
tissue-resident memory T cells; T cell infiltration of human cancer; microarray; bioinformatics; precision medicine
Funding
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [2015ZT9MXY_001, 2017MLC3NF_005]
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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.
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