Phenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy

Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contradiction of the 2 TINK clusters, we further tested cytokine functions of SELL + and TNFRSF7 + TINKs by single-cell secreting proteomics using a 32-cytokine panel. Consistently, SELL + TINK clusters were characterized by immuno-suppressive secretion patterns (IL10+). A low proportion of SELL + TINK cluster and low proportion of IL10 + secreting SELL + TINK cluster (single-cell secreting proteomics) were both associated with better progression-free survival time. These findings were validated in an independent cohort of 15 patients during 16-month follow-up. Overall, we identified a distinct immuno-suppressive TINK cell group, featuring IL10 + secreting and SELL expression with a strong relation to poor survival prognosis in TNBC patients post-NATI.

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Publication Details

Journal
Breast Cancer Research
Published
2025-04-03
DOI
https://doi.org/10.1186/s13058-025-02003-y
Citations
2
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
1.59

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article

Phenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy

Xin Qi, Guanqing Zhong, Yu Si Niu, Xiajie Lyu et al.
2 citations
Breast Cancer Research
Immune Cell Function and Interaction
1.59
article

Phenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy

Xin Qi, Guanqing Zhong, Yu Si Niu, Xiajie Lyu, Jiling Zeng, Yifei Ma, Fadian Ding, Jiacai Lin, Hong-Jun Zheng, Bocen Chen, Pengfei Zhu, Yongluo Jiang, Xinjia Wang, Weidong Wang, Li Jin, Jun Lü, Yue Ma, Jinjian Li, Tong Huang, Tingting He, Yi-Wei Xu, Youlong Wang
article en
2 citations

Abstract

Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contradiction of the 2 TINK clusters, we further tested cytokine functions of SELL + and TNFRSF7 + TINKs by single-cell secreting proteomics using a 32-cytokine panel. Consistently, SELL + TINK clusters were characterized by immuno-suppressive secretion patterns (IL10+). A low proportion of SELL + TINK cluster and low proportion of IL10 + secreting SELL + TINK cluster (single-cell secreting proteomics) were both associated with better progression-free survival time. These findings were validated in an independent cohort of 15 patients during 16-month follow-up. Overall, we identified a distinct immuno-suppressive TINK cell group, featuring IL10 + secreting and SELL expression with a strong relation to poor survival prognosis in TNBC patients post-NATI.

Breast Cancer ResearchVol. 27(1)
Fujian Medical University (CN), Sun Yat-sen University (CN), Shanxi Medical University (CN), Dallas County (US), BirdLife International (KE), Jacobi Medical Center (US), Chinese PLA General Hospital (CN), Shantou University (CN), Cancer Hospital of Shantou University Medical College (CN), First Affiliated Hospital of Shantou University Medical College (CN), Second Affiliated Hospital of Shantou University Medical College (CN), First Affiliated Hospital of Fujian Medical University (CN), Hainan General Hospital (CN), Hainan 301 Hospital (CN), Sun Yat-sen University Cancer Center (CN), Urumqi General Hospital of PLA (CN), First Affiliated Hospital of Zhengzhou University (CN), Shanxi Academy of Medical Sciences (CN), Hainan 301 Hospital (CN), Hainan Medical University (CN)
Basic and Applied Basic Research Foundation of Guangdong Province
Good health and well-being
Openalex Percentile: Top 18%
Immune Cell Function and Interaction
1.59
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