PD-1 blockade plus tyrosine kinase inhibitor remodels the tumor microenvironment in advanced renal cell carcinoma
neutrophil subset exhibiting immunosuppressive properties that is associated with poor clinical response. In vivo, pharmacologic inhibition of SAA enhanced sensitivity to ICI plus TKI combination therapy, while blockade of the CEACAM1-TIM-3 axis in humanized PD-1 mouse models significantly potentiated anti-PD-1 efficacy. Our study establishes a single-cell atlas of the aRCC tumor microenvironment under treatment pressure and identifies a previously unrecognized SAA-CEACAM1-TIM-3 axis driving drug resistance, highlighting potential targets to improve therapy efficacy.
Authors
- Weimin Ci (ORCID: https://orcid.org/0000-0002-4111-5360)
- Yezhen Tan (ORCID: https://orcid.org/0009-0008-1608-9843)
- Qingbo Huang (ORCID: https://orcid.org/0000-0003-2894-0187)
- Yan Huang (ORCID: https://orcid.org/0000-0002-1789-5088)
- Zhuoran Li (ORCID: https://orcid.org/0009-0005-7646-4391)
- Qiyang Liang
- Y. H. Zhou
- Liangyou Gu
- Baojun Wang
- Xu Zhang
- Qing Bi
- Xiubin Li
- Qi Zhang
- Yaohui Wang
- Xin Ma
- Chenfeng Wang
Institutions
- Nankai University (CN)
- Wenzhou Medical University (CN)
- Chinese PLA General Hospital (CN)
- Affiliated Eye Hospital of Wenzhou Medical College (CN)
- PLA Academy of Military Science (CN)
- Third Hospital of Changsha (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1038/s41467-026-70978-z
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China