Abstract

Background

Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT.

Methods

Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS.

Results

Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E−14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E−08). This association was not observed in low TMB patients.

Conclusions

We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.

Details

Title
Tumor immunogenomic signatures improve a prognostic model of melanoma survival
Author
Morales, Leah; Simpson, Danny; Ferguson, Robert; Cadley, John; Esteva, Eduardo; Monson, Kelsey; Vylyny Chat; Martinez, Carlos; Weber, Jeffrey; Osman, Iman; Kirchhoff, Tomas
Pages
1-11
Section
Research
Publication year
2021
Publication date
2021
Publisher
BioMed Central
e-ISSN
14795876
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2491330740
Copyright
© 2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.