2. Academic Validation
  3. Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti-angiogenic Therapy in Armored and Cold Tumors

Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti-angiogenic Therapy in Armored and Cold Tumors

  • Adv Sci (Weinh). 2025 Jan 17:e2409147. doi: 10.1002/advs.202409147.
Jie Mei 1 2,  Kai Yang 1 2,  Xinkang Zhang 1 2,  Zhiwen Luo 3,  Min Tian 1 2,  Hanfang Fan 4,  Jiahui Chu 1 2,  Yan Zhang 5,  Junli Ding 4,  Junying Xu 4,  Yun Cai 6,  Yongmei Yin 1 7
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 211166, P. R. China.
  • 2 The First Clinical Medicine College, Nanjing Medical University, Nanjing, Jiangsu, 211166, P. R. China.
  • 3 Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, P. R. China.
  • 4 Departments of Oncology, Wuxi People's Hospital, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, P. R. China.
  • 5 Departments of Gynecology, The Women's Hospital Affiliated to Jiangnan University, Wuxi, 214023, China.
  • 6 Central Laboratory, Changzhou Jintan First People's Hospital, The Affiliated Jintan Hospital of Jiangsu University, Changzhou, Jiangsu, 213200, P. R. China.
  • 7 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: 39823457 DOI: 10.1002/advs.202409147
Abstract

A previous study classifies solid tumors based on collagen deposition and immune infiltration abundance, identifying a refractory subtype termed armored & cold tumors, characterized by elevated collagen deposition and diminished immune infiltration. Beyond its impact on immune infiltration, collagen deposition also influences tumor angiogenesis. This study systematically analyzes the association between immuno-collagenic subtypes and angiogenesis across diverse Cancer types. As a result, armored & cold tumors exhibit the highest angiogenic activity in lung adenocarcinoma (LUAD). Single-cell and spatial transcriptomics reveal close interactions and spatial co-localization of fibroblasts and endothelial cells. In vitro experiments demonstrate that collagen stimulates tumor cells to express vascular endothelial growth factor A (VEGFA) and directly enhances vessel formation and endothelial cell proliferation through sex determining region Y box 18 (SOX18) upregulation. Collagen inhibition via multiple approaches effectively suppresses tumor angiogenesis in vivo. In addition, armored & cold tumors display superior responsiveness to anti-angiogenic therapy in advanced LUAD cohorts. Post-immunotherapy resistance, the transformation into armored & cold tumors emerges as a potential biomarker for selecting anti-angiogenic therapy. In summary, collagen deposition is shown to drive angiogenesis across various cancers, providing a novel and actionable framework to refine therapeutic strategies combining chemotherapy with anti-angiogenic treatments.

Keywords

anti‐angiogenic therapy; armored & cold tumor; collagen deposition; vascularization.

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