Single-Cell Profiling Reveals Sustained Immune Infiltration, Surveillance, and Tumor Heterogeneity in Infiltrative Basal Cell Carcinoma

Lingjuan Huang; Xianggui Wang; Shiyao Pei; Xin Li; Liang Dong; Xiaohui Bian; Hongyin Sun; Liping Jin; Huihui Hou; Wensheng Shi; Xiyuan Zhang; Lining Zhang; Shuang Zhao; Xiang Chen; Mingzhu Yin

doi:10.1016/j.jid.2023.04.020

Single-Cell Profiling Reveals Sustained Immune Infiltration, Surveillance, and Tumor Heterogeneity in Infiltrative Basal Cell Carcinoma

J Invest Dermatol. 2023 Nov;143(11):2283-2294.e17. doi: 10.1016/j.jid.2023.04.020. Epub 2023 May 17.

Authors

Affiliations

¹ Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Central South University, Changsha, China.
² Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Central South University, Changsha, China; Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Central South University, Changsha, China; Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Central South University, Changsha, China. Electronic address: yinmingzhu2008@126.com.

PMID: 37201777
DOI: 10.1016/j.jid.2023.04.020

Abstract

Infiltrative basal cell carcinoma (iBCC) is a particularly aggressive subtype of basal cell carcinoma that tends to progress and recur after surgery, and its malignancy is closely related to the tumor microenvironment. In this study, we performed a comprehensive single-cell RNA analysis to profile 29,334 cells from iBCC and adjacent normal skin. We found active immune collaborations enriched in iBCC. Specifically, SPP1⁺CXCL9/10^high macrophage 1 had strong BAFF signaling with plasma cells, and T follicular helper-like cells highly expressed the B-cell chemokine CXCL13. Heterogeneous proinflammatory SPP1⁺CXCL9/10^high macrophage 1 and angiogenesis-related SPP1⁺CCL2^high macrophage 1 were identified within the tumor microenvironment. Interestingly, we found an upregulation of major histocompatibility complex I molecules in fibroblasts in iBCC compared with those in adjacent normal skin. Moreover, MDK signals derived from malignant basal cells were markedly increased, and their expression was an independent factor in predicting the infiltration depth of iBCC, emphasizing its role in driving malignancy and remodeling the tumor microenvironment. In addition, we identified differentiation-associated SOSTDC1⁺IGFBP5⁺CTSV⁺ malignant basal subtype 1 and epithelial-mesenchymal transition-associated TNC⁺SFRP1⁺CHGA⁺ malignant basal subtype 2 cells. The high expression of malignant basal 2 cell markers was associated with the invasion and recurrence of iBCC. Altogether, our study helps to elucidate the cellular heterogeneity in iBCC and provides potential therapeutic targets for clinical research.