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Updated: Aug 14, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Immune checkpoint blockade sensitivity is linked to endogenous retroelement transcriptional changes in cancer
Mercedes Herrera1, Sajid A Marhon2, Zhihui Amy Liu1
1Princess Margaret Cancer Centre Toronto Canada.
Abstract:
Endogenous retrotransposable elements (EREs) can modulate immune responses. We explored ERE transcription in relation to response to immune checkpoint inhibition in advanced solid tumors. ERE expression was measured in pre and on-treatment samples from patients treated in a clinical trial with pembrolizumab. We evaluated immune cell infiltration and correlated ERE expression with interferon-stimulated gene profiles and cytolytic activity. Two independent datasets were retrospectively analyzed as external validation. ERE transcription, notably Alu followed by LINE elements, is upregulated in immunotherapy responders, and higher ERE expression correlates with durable clinical benefit and improved long-term outcomes. In responders, this dynamic increase correlates with CD8+ T cell infiltration and cytolytic activity, particularly during treatment. A trend towards increased A-to-I RNA editing was observed in responders. External validation in melanoma and non-small cell lung cancer cohorts confirmed a consistent pattern in ERE transcription. Therefore, ERE transcription is as a potential biomarker for personalized immunotherapy in solid tumors.
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