Research Paper|Volume 16, Issue 1|pp 568—592

Immune landscape and heterogeneity of cervical squamous cell carcinoma and adenocarcinoma

Binghan Liu^1,^2,³, Yashi Xu^1,^2,³, Bai Hu^2,³, Xiaole Song⁴, Shitong Lin^1,^2,³, Jiaxuan Wang⁵, Lingfang Wang⁶, Tian Chu^2,³, Ting Peng^1,^2,³, Miaochun Xu^1,^2,³, Wencheng Ding^2,³, Canhui Cao^2,³, Peng Wu^1,^2,³, Li Li²

¹Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China
²Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
³Cancer Biology Research Center (Key Laboratory of The Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430100, Hubei, China
⁴Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
⁵BGI-Shenzhen, Shenzhen 518083, Guangzhou, China
⁶Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang, China

* Equal contribution

Received: July 12, 2023Accepted: October 17, 2023Published: January 10, 2024

https://doi.org/10.18632/aging.205397

Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients’ prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.