SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors

Theron Palmer; Michael D Kessler; Xiaoshan M Shao; Archana Balan; Mark Yarchoan; Neeha Zaidi; Tamara Y Lopez-Vidal; Ali M Saeed; Jessica Gore; Nilofer S Azad; Elizabeth M Jaffee; Alexander V Favorov; Valsamo Anagnostou; Rachel Karchin; Daria A Gaykalova; Elana J Fertig; Ludmila Danilova

doi:10.1158/2767-9764.CRC-23-0309

SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors

Cancer Res Commun. 2024 Dec 1;4(12):3137-3150. doi: 10.1158/2767-9764.CRC-23-0309.

Authors

Theron Palmer^{1

2}, Michael D Kessler^{2

3}, Xiaoshan M Shao¹, Archana Balan¹, Mark Yarchoan^{2

3

4}, Neeha Zaidi^{2

3

4}, Tamara Y Lopez-Vidal^{2

3

4

5}, Ali M Saeed^{2

3

4}, Jessica Gore^{6

7}, Nilofer S Azad^{2

3

4}, Elizabeth M Jaffee^{2

3

4}, Alexander V Favorov^{2

3

4

8}, Valsamo Anagnostou^{3

4}, Rachel Karchin^{1

3}, Daria A Gaykalova^#^{3

6

7}, Elana J Fertig^#^{1

2

3

4

9}, Ludmila Danilova^#^{2

3

4}

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
² Convergence Institute, Johns Hopkins University, Baltimore, Maryland.
³ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
⁴ Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
⁵ Biochemistry, Cellular and Molecular Biology (BCMB) Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁶ Department of Otorhinolaryngology-Head and Neck Surgery, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland.
⁷ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland.
⁸ Laboratory of Systems Biology and Computational Genetics, Vavilov Institute of General Genetics, Moscow, Russia.
⁹ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland.

^# Contributed equally.

Abstract

SpliceMutr shows that splicing antigenicity changes in response to ICI therapies and that native modulation of the splicing machinery through mutations increases the contribution of splicing to the neoantigen load of some The Cancer Genome Atlas cancer subtypes. Future studies of the relationship between splicing antigenicity and immune checkpoint inhibitor response pan-cancer are essential to establish the interplay between antigen heterogeneity and immunotherapy regimen on patient response.

MeSH terms

Antigens, Neoplasm* / genetics
Antigens, Neoplasm* / immunology
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy / methods
Mutation
Neoplasms* / genetics
Neoplasms* / immunology
Neoplasms* / therapy
RNA Splicing

Substances

Antigens, Neoplasm
Immune Checkpoint Inhibitors