2. Academic Validation
  3. Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade

  • Cancer Commun (Lond). 2024 Mar 20. doi: 10.1002/cac2.12538.
Jie Mei 1 2,  Yun Cai 3,  Rui Xu 1 2,  Qing Li 4,  Jiahui Chu 1 2,  Zhiwen Luo 5,  Yaying Sun 6,  Yuxin Shi 7,  Junying Xu 7,  Di Li 8,  Shuai Liang 7,  Ying Jiang 9,  Jiayu Liu 9,  Zhiwen Qian 3,  Jiaofeng Zhou 10,  Mengyun Wan 10,  Yunlong Yang 11,  Yichao Zhu 10,  Yan Zhang 3 9,  Yongmei Yin 1 12
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
  • 2 The First Clinical Medicine College, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
  • 3 Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, P. R. China.
  • 4 Departments of Oncology, Xuzhou Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Xuzhou, Jiangsu, P. R. China.
  • 5 Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, P. R. China.
  • 6 Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
  • 7 Departments of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, P. R. China.
  • 8 Shanghai Outdo Biotech Co., Ltd., National Engineering Center for Biochip, Shanghai, P. R. China.
  • 9 Departments of Gynecology, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu, P. R. China.
  • 10 Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
  • 11 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P. R. China.
  • 12 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
PMID: 38507505 DOI: 10.1002/cac2.12538
Abstract

Background: Immune checkpoint blockade (ICB) has revolutionized the treatment of various Cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy.

Methods: We analyzed transcriptomic collagen activity and immune signatures in 649 patients with Cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 Cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in-house samples. Additionally, novel therapeutic targets were identified based on these established immuno-collagenic subtypes.

Results: Our categorization divided tumors into three subtypes: "soft & hot" (low collagen activity and high immune infiltration), "armored & cold" (high collagen activity and low immune infiltration), and "quiescent" (low collagen activity and immune infiltration). Notably, "soft & hot" tumors exhibited the most robust response to ICB therapy across various Cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple Cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7-H3), an available drug target, as strongly expressed in "armored & cold" tumors, relating with poor prognosis.

Conclusion: This study introduces histopathology-based universal immuno-collagenic subtypes capable of predicting ICB responses across diverse Cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with Cancer.

Keywords

collagen deposition; immune infiltration; immunotherapy; pan‐cancer; tumor microenvironment.

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