Spatial Transcriptional Dynamics of CD74⁺ B Cells in Tertiary Lymphoid Structures Drive Immune Evolution in Penile Squamous Cell Carcinoma

Penile squamous cell carcinoma (PSCC) is a malignancy characterized by a poor prognosis and lack of reliable biomarkers, presenting considerable therapeutic challenges. Tertiary lymphoid structures (TLSs) are critical modulators of antitumor immunity; however, the immunological dynamics, particularly the roles of B cells and their interactions with naive T cells in PSCC tissues, remain inadequately understood. This study integrates transcriptomic approaches, including spatial transcriptomics, single-cell sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq), and immunohistochemistry to elucidate the immune architecture of and functional mechanisms within TLSs. The results reveal a positive correlation between TLS density and patient survival, with CD74⁺ B cells tending to be enriched during early TLS formation. These cells exhibit strong immune activation and a propensity to differentiate into plasma cells. By engaging with naive T cells through HLA-DRA via ligand-receptor interactions, CD74⁺ B cells activate transcription factors, including NFKB1, NFKB2, NFATC1, NFATC2, FOS, and RUNX1, in naive T cells, thereby enhancing the immune response. Consequently, CD74⁺ B cells represent a compelling biomarker for and therapeutic target of PSCC, offering profound insights into the immunological mechanisms that drive PSCC progression and response to immunotherapy.

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Publication Details

Journal
Advanced Science
Published
2025-10-20
DOI
https://doi.org/10.1002/advs.202509742
Citations
2
Primary Topic
Genital Health and Disease
Type
article
Field-Weighted Citation Impact
4.01
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article

Spatial Transcriptional Dynamics of CD74⁺ B Cells in Tertiary Lymphoid Structures Drive Immune Evolution in Penile Squamous Cell Carcinoma

Jietian Jin, Hui Han, Zaishang Li, Jingya Liu et al.
2 citations
Advanced Science
Genital Health and Disease
4.01
article

Spatial Transcriptional Dynamics of CD74⁺ B Cells in Tertiary Lymphoid Structures Drive Immune Evolution in Penile Squamous Cell Carcinoma

Jietian Jin, Hui Han, Zaishang Li, Jingya Liu, Yujie Liang, D Chen, Xiheng Hu, Dongbin Wang, Chuangzhong Deng, Hongzhen Tang, Bonan Chen, Jing Li, Xueying Li, Zhengping Zuo, Ting Xue, Ru Yan, Xiao Xiao
article en
2 citations

Abstract

Penile squamous cell carcinoma (PSCC) is a malignancy characterized by a poor prognosis and lack of reliable biomarkers, presenting considerable therapeutic challenges. Tertiary lymphoid structures (TLSs) are critical modulators of antitumor immunity; however, the immunological dynamics, particularly the roles of B cells and their interactions with naive T cells in PSCC tissues, remain inadequately understood. This study integrates transcriptomic approaches, including spatial transcriptomics, single-cell sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq), and immunohistochemistry to elucidate the immune architecture of and functional mechanisms within TLSs. The results reveal a positive correlation between TLS density and patient survival, with CD74⁺ B cells tending to be enriched during early TLS formation. These cells exhibit strong immune activation and a propensity to differentiate into plasma cells. By engaging with naive T cells through HLA-DRA via ligand-receptor interactions, CD74⁺ B cells activate transcription factors, including NFKB1, NFKB2, NFATC1, NFATC2, FOS, and RUNX1, in naive T cells, thereby enhancing the immune response. Consequently, CD74⁺ B cells represent a compelling biomarker for and therapeutic target of PSCC, offering profound insights into the immunological mechanisms that drive PSCC progression and response to immunotherapy.

Advanced ScienceVol. 12(44)
Guangzhou University of Chinese Medicine (CN), Central South University (CN), Sun Yat-sen University (CN), Guangdong Medical College (CN), Chinese University of Hong Kong (HK), Dongguan University of Technology (CN), Southern University of Science and Technology (CN), The Seventh Affiliated Hospital of Sun Yat-sen University (CN), HKUST Shenzhen Research Institute (CN), ShenZhen People’s Hospital (CN), Prince of Wales Hospital (CN), Shenzhen KangNing Hospital (CN), Sun Yat-sen University Cancer Center (CN), Guangzhou Medical University Cancer Hospital (CN), Guizhou Provincial People's Hospital (CN), Xiangya Hospital Central South University (CN), Shenzhen Second People's Hospital (CN), Atotech (United States) (US), University of Hong Kong (HK), Guangzhou Medical University (CN)
Openalex Percentile: Top 6%
Genital Health and Disease
4.01
DOIOpen Access PDFOpenAlex
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