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Cited by 284

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Pharmacologic modulation of RNA splicing enhances anti-tumor immunity

Open access
Lu, Sydney X., De Neef, Emma, Thomas, James D., Sabio, Erich, Rousseau, Benoit, Gigoux, Mathieu, Knorr, David A., Greenbaum, Benjamin, Elhanati, Yuval, Hogg, Simon J., Chow, Andrew, Ghosh, Arnab, Xie, Abigail, Zamarin, Dmitriy, Cui, Daniel, Erickson, Caroline, Singer, Michael, Cho, Hana, Wang, Eric, Lu, Bin, Durham, Benjamin H., Shah, Harshal, Chowell, Diego, Gabel, Austin M., Shen, Yudao, Liu, Jing, Jin, Jian, Rhodes, Matthew C., Taylor, Richard E., Molina, Henrik, Wolchok, Jedd D., Merghoub, Taha, Diaz, Luis A., Abdel-Wahab, Omar, Bradley, Robert K.·2021·Cell
DOI 10.1016/j.cell.2021.05.038
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Abstract

SUMMARY While mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Splicing modulation inhibited tumor growth and enhanced checkpoint blockade in a manner dependent on host T cells and peptides presented on tumor MHC class I. Splicing modulation induced stereotyped splicing changes across tumor types, altering the MHC I-bound immunopeptidome to yield splicing-derived neoepitopes which trigger an anti-tumor T cell response in vivo. These data definitively identify splicing modulation as an untapped source of immunogenic peptides and provide a means to enhance response to checkpoint blockade that is readily translatable to the clinic. In Brief sentence: By provoking production of “neoantigens” that are recognized by immune cells, drugs that modulate RNA splicing can enhance cancer immunotherapy. Original, unedited In Brief (do not use): Here, we present definitive proof of concept that pharmacologic modulation of RNA splicing enhances anti-tumor immunity via the generation of endogenous, mis-spliced antigenic peptides and augments the efficacy of immune checkpoint blockade.

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Authors
Lu, S. X., De Neef, E., Thomas, J. D., Sabio, E., Rousseau, B., Gigoux, M., Knorr, D. A., Greenbaum, B., Elhanati, Y., Hogg, S. J., Chow, A., Ghosh, A., Xie, A., Zamarin, D., Cui, D., Erickson, C., Singer, M., Cho, H., Wang, E., Lu, B., Durham, B. H., Shah, H., Chowell, D., Gabel, A. M., Shen, Y., Liu, J., Jin, J., Rhodes, M. C., Taylor, R. E., Molina, H., Wolchok, J. D., Merghoub, T., Diaz, L. A., Abdel-Wahab, O., & Bradley, R. K.
Venue
Cell
Publisher
Elsevier BV
Published
2021-07
Volume
184
Issue
15
Pages
4032-4047.e31
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2021.05.038
OpenAlex
W3176618876
Cited by
284
References
47
FWCI
15.41
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. https://app.cochat.ai/papers/10.1016/j.cell.2021.05.038
The paper
Lu, S. X., De Neef, E., Thomas, J. D., Sabio, E., Rousseau, B., Gigoux, M., Knorr, D. A., Greenbaum, B., Elhanati, Y., Hogg, S. J., Chow, A., Ghosh, A., Xie, A., Zamarin, D., Cui, D., Erickson, C., Singer, M., Cho, H., Wang, E., . . . Bradley, R. K. (2021). Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. Cell. https://doi.org/10.1016/j.cell.2021.05.038

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.