High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer

Jie Mei; Yun Cai; Hongjun Zhu; Ying Jiang; Ziyi Fu; Junying Xu; Lingyan Chen; Kai Yang; Jinlu Zhao; Chenghu Song; Yan Zhang; Wenjun Mao; Yongmei Yin

doi:10.1038/s41523-024-00618-6

High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer

NPJ Breast Cancer. 2024 Jan 27;10(1):11. doi: 10.1038/s41523-024-00618-6.

Authors

Jie Mei^#^{1

2

3}, Yun Cai^#⁴, Hongjun Zhu^#⁵, Ying Jiang^#⁶, Ziyi Fu¹, Junying Xu³, Lingyan Chen⁴, Kai Yang^{1

2

3}, Jinlu Zhao⁷, Chenghu Song⁸, Yan Zhang^{9

10}, Wenjun Mao¹¹, Yongmei Yin^{12

13}

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 211166, China.
² The First Clinical Medicine College, Nanjing Medical University, Wuxi, 214023, China.
³ Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China.
⁴ Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, 214023, China.
⁵ Department of Oncology, Nantong Third People's Hospital Affiliated to Nantong University, Nantong, 226006, China.
⁶ Department of Gynecology, The Obstetrics and Gynecology Hospital Affiliated to Jiangnan University, Wuxi, 214023, China.
⁷ Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
⁸ Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China.
⁹ Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center of Nanjing Medical University, Wuxi, 214023, China. fuyou2007@126.com.
¹⁰ Department of Gynecology, The Obstetrics and Gynecology Hospital Affiliated to Jiangnan University, Wuxi, 214023, China. fuyou2007@126.com.
¹¹ Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China. maowenjun1@njmu.edu.cn.
¹² Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 211166, China. ymyin@njmu.edu.cn.
¹³ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China. ymyin@njmu.edu.cn.

^# Contributed equally.

Abstract

Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.