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Updated: May 7, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma

Ameish Govindarajan1,2, Nathaniel Hansen3, Benjamin D Mercier1

  • 1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.

Journal for Immunotherapy of Cancer
|May 5, 2026
PubMed
Abstract

Insights

Aberrant splicing in metastatic renal cell carcinoma (mRCC) can predict response to immune checkpoint inhibitors and targeted therapies. Specific splicing events and derived neoantigens offer new therapeutic targets for mRCC treatment.

Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Aberrant alternative splicing (AS) is linked to cancer progression.
  • The role of AS in metastatic renal cell carcinoma (mRCC) and its impact on treatment response is not well understood.

Purpose of the Study:

  • To identify AS events associated with clinical benefits in mRCC patients treated with immune checkpoint inhibitors (ICIs) and targeted therapies.
  • To explore the potential of AS events to generate neoantigens for novel therapeutic strategies.

Main Methods:

  • Retrospective analysis of 101 mRCC patients undergoing RNA sequencing.
  • Differential splicing analysis between responders and non-responders to ICIs and targeted therapies.
  • Prediction of neoantigen generation from AS events and MHC class I binding.

Main Results:

  • 10 aberrant splice events were specific to mRCC.
  • 461 and 253 differentially spliced events were identified in ICI and targeted therapy cohorts, respectively, with intron retention being predominant.
  • 13 unique AS events, including PTPN6 and ACTN1, were enriched in responders. AS events in IFFO1 and ZNF692 showed high neoantigen potential.
  • High splice burden correlated with an immunogenic tumor microenvironment.

Conclusions:

  • Intron retention in mRCC serves as a potential biomarker for predicting treatment response.
  • AS-derived neoantigens represent promising targets for adoptive cell therapy in mRCC.
Keywords:
BiomarkerImmune Checkpoint InhibitorRenal Cell CarcinomaTumor microenvironment - TME

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