Tumor-associated NK Cells Regulate Distinct CD8+ T-cell Differentiation Program in Cancer and Contribute to Resistance against Immune Checkpoint Blockers
Although NK cells are traditionally viewed as antitumor effectors, our study uncovers their unexpected suppressive role in CD8+ T cell-based immunotherapy. By competing for cytokines, they disrupt retinoic acid receptor α-driven CD8+ T-cell differentiation and limit ICB efficacy. Clinically, reduced NK cell presence is associated with an enhanced immunotherapy response. See related commentary by Galvez-Cancino et al., p. 1777 See related article by Pozniak et al., p. 1819.
Authors
- Zihai Li (ORCID: https://orcid.org/0000-0003-4603-927X)
- Christin E. Burd (ORCID: https://orcid.org/0000-0002-7919-3954)
- Bethany L. Mundy-Bosse (ORCID: https://orcid.org/0009-0004-7397-7653)
- Jean‐Christophe Marine (ORCID: https://orcid.org/0000-0003-2433-9837)
- Kyeong Joo Jung (ORCID: https://orcid.org/0000-0002-0582-1583)
- Parker Kronen (ORCID: https://orcid.org/0009-0007-6004-0740)
- Yi Wang (ORCID: https://orcid.org/0000-0002-4046-9511)
- No‐Joon Song (ORCID: https://orcid.org/0009-0002-0947-0597)
- Qin Ma (ORCID: https://orcid.org/0000-0002-3264-8392)
- Jayajit Das (ORCID: https://orcid.org/0000-0001-9649-4698)
- Niccolò Roda (ORCID: https://orcid.org/0000-0003-2798-2035)
- Hyeongseon Jeon (ORCID: https://orcid.org/0000-0002-3539-4332)
- Juan Xie (ORCID: https://orcid.org/0000-0002-4170-9273)
- Joanna Poźniak (ORCID: https://orcid.org/0000-0001-5739-1098)
- Nigel Cox (ORCID: https://orcid.org/0000-0001-6778-8339)
- Anjun Ma (ORCID: https://orcid.org/0000-0001-6269-398X)
- Nicholas Denko (ORCID: https://orcid.org/0000-0001-6875-734X)
- Anqi Li (ORCID: https://orcid.org/0000-0002-4590-8739)
- David P. Carbone (ORCID: https://orcid.org/0000-0003-3002-1921)
- William Edgar Carson (ORCID: https://orcid.org/0000-0001-7024-7533)
- Brian Riesenberg (ORCID: https://orcid.org/0000-0001-7358-3479)
- Darren Wethington (ORCID: https://orcid.org/0000-0002-3170-8998)
- Dongjun Chung (ORCID: https://orcid.org/0000-0002-8072-5671)
- Kelsi Reynolds (ORCID: https://orcid.org/0009-0001-8201-7644)
- Tong Xiao (ORCID: https://orcid.org/0009-0007-7996-4134)
Institutions
- Nationwide Children's Hospital (US)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- The Ohio State University Wexner Medical Center (US)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Cancer Genetics (United States) (US)
- The Ohio State University (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-06-18
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-1232
- Citations
- 14
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 11.16
Funders
- American Cancer Society
- Pelotonia
- National Institutes of Health
- National Human Genome Research Institute
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases