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Corrigendum Open Access | 10.1172/JCI192014

Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures

Chester J. Kao, Soren Charmsaz, Stephanie L. Alden, Madelena Brancati, Howard L. Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman, Ervin Griffin, Mari Nakazawa, Hua-Ling Tsai, Ludmila Danilova, Chris Thoburn, Jennifer Gizzi, Nicole E. Gross, Alexei Hernandez, Erin M. Coyne, Sarah M. Shin, Jayalaxmi Suresh Babu, George W. Apostol, Jennifer Durham, Brian J. Christmas, Maximilian F. Konig, Evan J. Lipson, Jarushka Naidoo, Laura C. Cappelli, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie Brahmer, Jean Hoffman-Censits, Tanguy Y. Seiwert, Rachel Garonce-Hediger, Aditi Guha, Sanjay Bansal, Laura Tang, Elizabeth M. Jaffee, G. Scott Chandler, Rajat Mohindra, Won Jin Ho, and Mark Yarchoan

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Published March 17, 2025 - More info

Published in Volume 135, Issue 6 on March 17, 2025
J Clin Invest. 2025;135(6):e192014. https://doi.org/10.1172/JCI192014.
© 2025 Kao et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 17, 2025 - Version history
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Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures
Chester J. Kao, … , Won Jin Ho, Mark Yarchoan
Chester J. Kao, … , Won Jin Ho, Mark Yarchoan
In a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early immunotherapy treatment was associated with the development of clinically relevant irAEs but not antitumor responses.
Clinical Medicine Oncology Article has an altmetric score of 82

Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures

Abstract

BACKGROUND Immune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pan-tumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies.METHODS In an observational study, we prospectively collected blood samples and performed regular clinical evaluations for irAEs in patients receiving ICI therapy as standard of care for solid tumors. We performed in-parallel analysis of cytokines by Luminex immunoassay and circulating immune cells by cytometry by time-of-flight (CyTOF) at baseline and on treatment to investigate mechanisms of irAEs.RESULTS We enrolled 111 patients, of whom 40.5% developed a symptomatic irAE (grade ≥ 2). Development of a grade ≥ 2 irAE was positively associated with the use of combination ICI and a history of an autoimmune disorder. Early changes in T helper 17 (Th17) (IL-6, IL-17f), type 2 (IL-5, IL-13, IL-25), and type 1 (TNF-α) cytokine signatures and congruent on-treatment expansions of Th17 and Th2 effector memory (Th2EM) T cell populations in peripheral blood were positively associated with the development of grade ≥2 irAEs. IL-6 levels were also associated with inferior cancer-specific survival and overall survival.CONCLUSIONS In a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early ICI treatment was associated with the development of clinically relevant irAEs but not antitumor responses, providing possible targets for monitoring and therapeutic interventions.FUNDING Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, the NCI SPORE in Gastrointestinal Cancers (P50 CA062924), NCI grant (R50CA243627 to LD), the NIH Center Core Grant (P30 CA006973), Swim Across America (to MY), NIAMS (K23AR075872 to LC), and imCORE-Genentech grant 137515 (to Johns Hopkins Medicine on behalf of MY).

Authors

Chester J. Kao, Soren Charmsaz, Stephanie L. Alden, Madelena Brancati, Howard L. Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman, Ervin Griffin, Mari Nakazawa, Hua-Ling Tsai, Ludmila Danilova, Chris Thoburn, Jennifer Gizzi, Nicole E. Gross, Alexei Hernandez, Erin M. Coyne, Sarah M. Shin, Jayalaxmi Suresh Babu, George W. Apostol, Jennifer Durham, Brian J. Christmas, Maximilian F. Konig, Evan J. Lipson, Jarushka Naidoo, Laura C. Cappelli, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie Brahmer, Jean Hoffman-Censits, Tanguy Y. Seiwert, Rachel Garonce-Hediger, Aditi Guha, Sanjay Bansal, Laura Tang, Elizabeth M. Jaffee, G. Scott Chandler, Rajat Mohindra, Won Jin Ho, Mark Yarchoan

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Original citation: J Clin Invest. 2024;134(20):e176567. https://doi.org/10.1172/JCI176567

Citation for this corrigendum: J Clin Invest. 2025;135(6):e192014. https://doi.org/10.1172/JCI192014

The authors recently became aware of errors in the display of box and whisker plots in Figure 4, C and D, Figure 5E, and Figure 7, C and D, and Supplemental Figures 1, 2, and 3, which resulted in data points beyond the tail to appear as double points rather than single points. The authors have stated that none of the underlying data, statistical analyses, results, or conclusions of the article are affected. The authors have provided the correct figure panels below. The HTML and PDF files have been updated to reflect the changes.

Figure 4

Figure 5

Figure 7

The authors regret the errors.

Footnotes

See the related article at Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures.

Version history
  • Version 1 (March 17, 2025): Electronic publication
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